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Animal and human studies have shown that greatly increasing the amount of fish oil [rich in long-chain (n-3) PUFA] in the diet can decrease lymphocyte functions. The effects of a more modest provision of long-chain (n-3) PUFA and whether eicosapentaenoic acid (20:5) and docosahexaenoic acid (22:6) have the same effects as one another are unclear. Whether the position of 20:5 or 22:6 in dietary triacylglycerols (TAG) influences their incorporation into immune cells and their subsequent functional effects is not known. In this study, male weanling rats were fed for 6 wk one of 9 diets that contained 178 g lipid/kg and that differed in the type of (n-3) PUFA and in the position of these in dietary TAG. The control diet contained 4.4 g alpha-linolenic acid (18:3)/100 g total fatty acids. In the other diets, 20:5 or 22:6 replaced a portion (50 or 100%) of 18:3, and were in the sn-2 or the sn-1(3) position of dietary TAG. There were significant dose-dependent increases in the proportion of 20:5 or 22:6 in spleen mononuclear cell phospholipids when 20:5 or 22:6 was fed. These increases were at the expense of arachidonic acid and were largely independent of the position of 20:5 or 22:6 in dietary TAG. Spleen lymphocyte proliferation increased dose dependently when 20:5 was fed in the sn-1(3) position of dietary TAG. There were no significant differences in interleukin-2, interferon-gamma or interleukin-10 production among spleen cells from rats fed the different diets. Prostaglandin E(2) production by spleen mononuclear cells was decreased by inclusion of either 20:5 or 22:6 in the diet in the sn-1(3) position. Thus, incorporation of 20:5 or 22:6 into spleen mononuclear cell phospholipids is not influenced by the position in dietary TAG. However, the pattern of incorporation may be influenced, and there are some differential functional effects of the position of long-chain (n-3) PUFA in dietary TAG. A moderate increase in the intake of 20:5 at the sn-1(3) position of dietary TAG increases lymphocyte proliferation.

The effects of altering the type of n-3 polyunsaturated fatty acid (PUFA) in the mouse diet on the ability of monocytes and neutrophils to perform phagocytosis were investigated. Male weanling mice were fed for 7 d on one of nine diets which contained 178 g lipid/kg and which differed in the type of n-3 PUFA and in the position of these in dietary triacylglycerol (TAG). The control diet contained 4.4 g alpha-linolenic acid/100 g total fatty acids. In the other diets, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) replaced a proportion (50 or 100 %) of the alpha-linolenic acid, and were in the sn-2 or the sn-1(3) position of dietary TAG. There were significant increases in the content of n-3 PUFA in spleen-cell phospholipids when EPA or DHA was fed. These increases were largely independent of the position of EPA or DHA in dietary TAG except when EPA was fed at the highest level, when the incorporation was greater when it was fed in the sn-2 than in the sn-1(3) position. There was no significant effect of dietary DHA on monocyte or neutrophil phagocytic activity. Dietary EPA dose-dependently decreased the number of monocytes and neutrophils performing phagocytosis. However, when EPA was fed in the sn-2 position, the ability of active monocytes or neutrophils to engulf bacteria was increased in a dose-dependent fashion. This did not occur when EPA was fed in the sn-1(3) position. Thus, there appears to be an influence of the position of EPA, but not of DHA, in dietary TAG on its incorporation into cell phospholipids and on the activity of phagocytic cells.

Objectives: To evaluate a system of prehospital thrombolysis, delivered by paramedics, in meeting the national service framework's targets for the management of acute myocardial infarction., Design: Prospective observational cohort study comparing patients with suspected acute myocardial infarction considered for thrombolysis in the prehospital environment with patients treated in hospital., Setting: The catchment area of a large teaching hospital, including urban and rural areas., Participants: 201 patients presenting concurrently over a 12 month period who had changes to the electrocardiogram that were diagnostic of acute myocardial infarction or who received thrombolysis for suspected acute myocardial infarction., Main Outcome Measures: Time from first medical contact to initiation of thrombolysis (call to needle time), number of patients given thrombolysis appropriately, and all cause mortality in hospital., Results: The median call to needle time for patients treated before arriving in hospital (n=28) was 52 (95% confidence interval 41 to 62) minutes. Patients from similar rural areas who were treated in hospital (n=43) had a median time of 125 (104 to 140) minutes. This represents a median time saved of 73 minutes (P < 0.001). Sixty minutes after medical contact 64% of patients (18/28) treated before arrival in hospital had received thrombolysis; this compares with 4% of patients (2/43) in a cohort from similar areas. Median call to needle time for patients from urban areas (n=107) was 80 (78 to 93) minutes. Myocardial infarction was confirmed in 89% of patients (25/28) who had received prehospital thrombolysis; this compares with 92% (138/150) in the two groups of patients receiving thrombolysis in hospital., Conclusions: Thrombolysis delivered by paramedics with support from the base hospital can meet the national targets for early thrombolysis. The system has been shown to work well and can be introduced without delay.

Effects of the conjugated linoleic acid (CLA) isomers cis-9, trans-11 (c9,t11 CLA) and trans-10, cis-12 (t10,c12 CLA) on lipid metabolism and markers of peroxisome proliferation were investigated in hamsters fed on purified diets containing 30% energy as fat and 0.1 g cholesterol/kg for 8 weeks. Four groups (n 32 each) received diets without CLA (control), with a mixture of equal amounts of c9,t11 and t10,c12 CLA (CLA mix), with c9,t11 CLA, and with t10,c12 CLA. The total amount of CLA isomers was 1.5% energy of 6.6g/ kg diet. CLA was incorporated into glycerides and exchanged for linoleic acid in the diet. Compared with the control, the CLA mix and t10,c12 CLA decreased fasting values of LDL- (21 and 18% respectively) and HDL-cholesterol (8 and 11%), increased VLDL-triacylglycerol (80 and 61%, and decreased epididymal fat pad weights (9 and 16%), whereas c9,t11 CLA had no significant effects. All CLA preparations increased liver weight, but not liver lipids. However, the increase in liver weight was much less in the c9,t11 CLA group (8%) than in the other two groups (25%) and might have been caused by the small amount of t10,c12 CLA present in the c9,t11 CLA preparation. Liver histology revealed that increased weight was due to hypertrophy. Markers of peroxisome proliferation, such as cyanide-insensitive palmitoyl CoA oxidase (EC 1.3.3.6) and carnitine acetyl transferase (EC 2.3.1.7) activities, were not increased by CLA. Both c9,t11 CLA and t10,c12 CLA were incorporated into phospholipids and triacylglycerols, but t10,c12 CLA only about half as much as c9,t11 CLA. In addition, linoleic acid and linolenic acid concentrations were lower in lipids of the t10,c12 CLA group compared with the c9,t11 CLA group. These data suggest that t10,c12 CLA stimulated the oxidation of all C18 polyunsaturated fatty acids. The results indicate that the t10,c12 CLA isomer, and not the so-called natural CLA isomer (c9,t11), is the active isomer affecting lipid levels in hamsters.

1,3-Oleoyl-2-palmitoylglycerol (OPO), an important structured triglyceride in infant nutrition, was synthesized by a two-step process in high yields and purity using sn1,3-regiospecific lipases. In the first step, tripalmitin (TP) was subjected to an alcoholysis reaction in an organic solvent catalyzed by sn1,3-regiospecific lipases yielding the corresponding 2-monopalmitin (2-MP). The 2-MP was isolated in up to 85% yield and >95% purity by crystallization and esterified in the second step with oleic acid using the same lipases to form the structured triglyceride OPO in up to 78% yield containing 96% palmitic acid in the sn2-position. Water activity, solvent, as well as carrier for lipase immobilization strongly influenced the yield and purity of products in both steps. The best results were achieved with lipases from Rhizomucor miehei and Rhizopus delemar immobilized on EP 100 and equilibrated to a water activity of 0.43. Special emphasis was given to develop this process in solvents that are allowed to be used in foodstuffs and to perform the second step in a solvent-free system., (Copyright 1999 John Wiley & Sons, Inc.)

Aims: Resting plasma levels of atrial natriuretic peptide and B-type natriuretic peptide rise with left ventricular dysfunction, but little is known about effects of cardiac ischaemia on atrial natriuretic peptide and B-type natriuretic peptide levels during exercise. We investigated exercise levels of atrial natriuretic peptide and B-type natriuretic peptide in patients with suspected angina to determine whether these measurements could improve non-invasive assessment of coronary disease severity., Methods and Results: One hundred patients performed an exercise test (Bruce protocol) within 2 weeks of coronary angiography. Plasma levels of atrial natriuretic peptide and B-type natriuretic peptide were measured at rest and at peak exercise. Multivariate regression analysis was used to assess effects of age, sex, coronary anatomy, exercise time and ventricular function on atrial natriuretic peptide and B-type natriuretic peptide levels. Increasing age and female sex were significantly associated with higher resting atrial natriuretic peptide levels; age alone was associated with higher exercise atrial natriuretic peptide levels. As expected, left ventricular end-diastolic pressure and disease of left anterior descending and circumflex coronary arteries were associated with increased resting B-type natriuretic peptide levels. However, the usual rise in B-type natriuretic peptide levels during exercise was independently reduced by disease of the right coronary artery., Conclusion: This paradoxical effect of right coronary artery disease limits the value of natriuretic peptide measurements as predictors of coronary disease severity. Impaired release of B-type natriuretic peptide may reduce exercise tolerance in patients with right coronary artery disease.

Large-scale trials of angiotensin converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) suggest that the benefits are greatest in patients with left ventricular (LV) dysfunction. However, early evaluation of LV function in all patients after AMI by current methods can be difficult due to a lack of resources and skilled personnel. Thus a clinical algorithm that could be used at the bedside to reliably identify patients with a left ventricular ejection fraction (LVEF) < or = 40% would be helpful as an occasional alternative to echocardiography. We have devised such an algorithm based on the presence of one of: (i) clinical signs of heart failure; (ii) an index Q-wave anterior myocardial infarction; (iii) lack of thrombolytic therapy when there is a history of two or more previous myocardial infarctions and a CK rise > 1000 U/l. We tested this new algorithm prospectively in the coronary care units of two hospitals (one UK and one USA). In the UK centre, the sensitivity and specificity of the algorithm at identifying patients with a LVEF < or = 40% were 82% and 72%, respectively. In the US centre, the sensitivity of the algorithm was 91% and the specificity 78% at identifying patients with LV dysfunction. We have validated a simple clinical algorithm which can be used at the bedside for identifying patients who would benefit from an ACE inhibitor after AMI.

Concomitant coronary artery disease often occurs in patients with peripheral vascular disease, but it may be asymptomatic. Despite being asymptomatic, cardiovascular events are the main source of morbidity and mortality in this group of patients. Dipyridamole thallium scintigraphy has been shown to be of prognostic value in patients with peripheral vascular disease and symptomatic coronary artery disease, but its effect on the long-term outcome in the asymptomatic group of patients is less defined. Eighty-four consecutive patients with peripheral vascular disease and no symptoms of coronary artery disease were therefore evaluated by clinical assessment, dipyridamole thallium imaging, radionuclide ventriculography, and cardiac catheterization and followed for a mean of 66 months. Abnormal perfusion patterns were found on thallium scintigraphy in 48 patients (57%); fixed, mixed, and reversible defects were present in 14 (17%), 11 (13%), and 23 (27%) patients, respectively. Significant coronary artery disease was present in 52 patients (69%) and mean left ventricular ejection fraction was 44%. During the follow-up period, 23 patients had a cardiac event (nonfatal myocardial infarction or cardiac death). Univariate analysis of 15 clinical, scintigraphic, radionuclide, and angiographic variables revealed that age, angiographic extent of coronary artery disease, and an abnormal thallium scan were significant predictors of subsequent cardiac events. Multivariate stepwise logistic regression analyses selected fixed and mixed thallium defects and diffuse coronary artery disease as the only significant independent predictors of outcome. Thus, the present study shows the value of dipyridamole thallium scintigraphy as a valuable prognostic indicator for long-term event-free survival in a cohort of patients with peripheral vascular disease and no history or symptoms of coronary artery disease.

Although elevations of plasma atrial natriuretic peptide (ANP) concentrations have been shown to have prognostic significance in patients after acute myocardial infarction (AMI), the relation between plasma levels of B-type natriuretic peptide (BNP) and cardiovascular mortality remains unknown. To test the prognostic value of plasma ANP and BNP after AMI, plasma concentrations were measured a mean of 3 days after infarction in 75 patients. During a median follow-up of 19.7 months, 14 patients (18.4%) died of cardiovascular causes. On univariate analysis, plasma ANP and BNP, Killip class, modified Peel index, left ventricular ejection fraction, and presence of left ventricular failure were all associated with cardiovascular mortality. In contrast, plasma ANP was the only variable that correlated with the development of symptomatic heart failure and hospitalization. For the combined end point of cardiovascular mortality, symptomatic heart failure, and hospitalization, plasma neurohormones were the only variables of predictive value. By stepwise regression analysis, plasma BNP was the only significant independent predictor of cardiovascular mortality (p = 0.001), whereas plasma ANP identified patients at risk of symptomatic heart failure and hospitalization (p = 0.002 and 0.019, respectively). This study indicates that plasma BNP measured after AMI is a powerful neurohormonal predictor of subsequent cardiovascular mortality, whereas plasma ANP correlates better with the development of symptomatic heart failure and hospitalization. Routine measurement of both of these peptides in the period immediately after an AMI may provide a simple means of risk stratification with different information gained from each peptide.

Free radicals (FR) are a highly reactive chemical species which have been implicated in the pathogenesis of reperfusion injury. Experimental models of reperfusion injury have demonstrated that FR scavengers improve myocardial salvage and thus it has been postulated that they may be of benefit in acute myocardial infarct (MI) patients treated with thrombolysis. Previous studies of FR activity post MI have focused on the immediate post reperfusion period; the present study investigates FR activity in post MI patients over a longer time span. Free radicals have a very short half-life and in clinical studies their activity is usually assessed indirectly by measuring either the level of FR reaction products such as malondialdehyde (MDA) or FR scavengers such as plasma thiols (PSH). In the presence of increased FR activity MDA levels increase and PSH levels decrease. Twenty-two acute MI patients had blood samples taken on admission, day 7 and day 21 post MI for measurement of MDA and PSH levels. On day 7 post MI a significant increase in MDA was detected P = 0.0001 (Sign test) (median change +2.1 mumol.l) and a significant decrease was detected in PSH P = 0.04 (Sign test) (median change, -38 mumol.l-1). No significant differences were detected between admission and day 21 levels of MDA and PSH. This study demonstrates the presence of enhanced FR activity at a later time point than has previously been recognised. White blood cells utilise FRs during phagocytosis and the late rise in FR activity detected in this study may reflect white blood cell removal of necrotic myocardium.

The mechanism(s) causing high levels of plasma atrial natriuretic factor (ANF) in cardiac allograft recipients is(are) unclear. The kidney is important for the clearance of ANF and renal function may decline with cyclosporin A therapy in these patients. The relationship between plasma ANF level and renal function and also the pharmacokinetics of a continuous infusion of ANF (15.5 ng.kg-1.min-1 for 60 min) was examined in 6 cardiac allograft recipients on cyclosporin A therapy. Resting plasma ANF levels were significantly higher in these patients than in 8 healthy subjects (71 vs. 21 ng.l-1). Both effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were significantly lower in these patients than in healthy subjects (215 vs. 617 ml.min-1 and 55 vs. 102 ml.min-1 respectively). There was a significant inverse correlation between plasma ANF and ERPF (r = -0.86) and between plasma ANF and GFR (r = -0.81). During the period of ANF infusion, steady state plasma ANF levels were significantly higher in cardiac allograft recipients. Total body clearance of ANF was marginally lower in these patients than in healthy subjects (60 vs. 10.0 l.min-1) although this difference did not reach statistical significance. Derived endogenous secretion rate of ANF was threefold higher in patients when compared to healthy subjects (633 vs. 208 ng.min-1). We have therefore shown that cardiac allograft recipients on cyclosporin A have elevated plasma ANF levels and also decreased renal function. Pharmacokinetic analysis have shown that this increase in plasma ANF levels is due more to increased ANF secretion than to decreased ANF clearance in these patients.

Objective: The SAVE study showed that captopril improves mortality in patients with left ventricular dysfunction after myocardial infarction and that this benefit occurred even in patients with no clinically overt heart failure. On the basis of this, it seems important to identify correctly which patients have left ventricular dysfunction after a myocardial infarction. The objective was to compare various methods of identifying patients with left ventricular dysfunction (left ventricular ejection fraction, LVEF, < or = 40%) after acute myocardial infarction. The methods compared were echocardiography (quantitative and qualitative visual assessment), clinical evaluation (subjective assessment and three clinical score methods), and measurement of plasma concentrations of cardiac natriuretic peptide hormones (atrial and brain natriuretic peptides, ANP and BNP)., Design: Cross sectional study of left ventricular function in patients two to eight days after acute myocardial infarction., Setting: Coronary care unit of a teaching hospital., Patients: 75 survivors of a recent myocardial infarction aged 40 to 88 with no history of cardiac failure and without cardiogenic shock at the time of entry to the study., Main Outcome Measures: Sensitivities and specificities of the various methods of detecting left ventricular dysfunction were calculated by comparing them with a cross sectional echocardiographic algorithm for LVEF., Results: Clinical impression was poor at identifying LVEF < 40% (sensitivity 46%). Clinical scoring improved this figure somewhat (modified Peel index sensitivity 64%). Qualitative visual assessment echocardiography was a more sensitive method (sensitivity 82%) for detecting LVEF < 40%. Plasma BNP concentration was also a sensitive measure for detecting left ventricular dysfunction (sensitivity 84%) but plasma ANP concentration was much poorer (sensitivity 64%)., Conclusion: Left ventricular dysfunction is easily and reliably detected by echocardiographic measurement of LVEF and also by a quick qualitative echocardiographic assessment but is likely to be missed by clinical assessment alone. High concentrations of plasma BNP maybe another useful indicator of left ventricular dysfunction, particularly in hospitals where not all patients can be screened by echocardiography or radionuclide ventriculography after myocardial infarction.

The effect of the injection of additional thallium after a redistribution study and prior to a further resting study was evaluated in 21 patients with angiographically proven coronary artery disease. Using dipyridamole as the stress mechanism, the studies were carried out tomographically and the results analysed quantitatively with the Bull's-eye technique. Two patients had normal scans. Of the remaining 19, 11 patients had a perfusion defect which appeared irreversible on redistribution imaging. However, six of these patients demonstrated improved or normal uptake after the second injection of thallium. Of the eight patients with a reversible defect, two revealed considerably greater reversibility after reinjection. These results indicate that the reinjection of thallium prior to the resting study significantly (P < 0.02) improves the detection rate of ischaemia during dipyridamole thallium tomography.

Objectives: To determine whether plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor antigen, and prostacyclin stimulating factor and plasminogen activator inhibitor activity show circadian variation in men with ischaemic heart disease., Design: Blood samples were obtained every four hours for 24 hours from 10 men with ischaemic heart disease. The men were ambulant from 08:10 until 00:00 when they went to bed and they remained in bed until 08:00 the following morning., Patients: Ten men with positive diagnostic exercise tolerance tests with no significant past history, who were not regularly taking any medical treatment except for glyceryl trinitrate., Results: There was significant circadian variation in plasminogen activator inhibitor activity (p = 0.001) (peak value 04:00 and trough value 20:00), but not in plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor, or prostacyclin stimulating factor., Conclusion: Men with ischaemic heart disease showed a significant circadian variation in fibrinolysis. The combination of peak values of plasminogen activator inhibitor activity and failure of plasma concentrations of tissue plasminogen activator antigen to increase in the early morning must predispose to thrombosis at this time. The circadian variation in fibrinolysis may contribute to the increased incidence of myocardial infarction in the morning.

Markers suggestive of enhanced free radical (FR) activity have been demonstrated in patients with chest pain and normal coronary angiograms. This may be of pathogenetic importance because FRs impair vascular relaxation and are generated following episodes of myocardial ischaemia/reperfusion. Fifteen patients with angina pectoris, normal coronary angiograms and either a positive exercise tolerance test and/or abnormal dipyridamole thallium tomogram were studied along with 15 age-, sex- and smoking-matched controls. A peripheral venous blood sample was obtained to measure the following FR markers: malondialdehyde, plasma thiols, red blood cell glutathione and superoxide dismutase. No significant differences were detected in the levels of any of the FR markers between either the group of 15 patients with chest pain and normal angiograms or the subgroup with positive exercise tolerance tests when compared to the controls. There is therefore no evidence of enhanced FR activity in patients with chest pain and normal coronary angiograms in peripheral venous blood samples.

The fibrinolytic activity of blood has a circadian variation with increased thrombotic tendency in the morning. This may be a contributory factor to the circadian variation in the time of onset of thrombotic events. However, there has recently been increasing interest to the role of the white blood cells (WBC) and free radicals (FRs) in thrombosis. We have previously reported a circadian variation in WBC aggregation and FR status in normal volunteers. No one has yet studied possible circadian variations in these parameters in patients with stable ischaemic heart disease (IHD). Ten men with stable IHD had blood samples collected at four-hourly intervals from midday until midday the following day. The patients were ambulant until midnight at which time they went to bed and remained in bed until 0800 h. The following were measured on each sample: WBC aggregation, malondialdehyde (MDA) which is a product of lipid peroxidation by FRs; the FR scavengers, plasma thiol (PSH), red cell glutathione (GSH) and superoxide dismutase (SOD) which are all altered in the presence of increased FR activity. WBC aggregation and PSH had significant circadian variations, P < 0.015 and P < 0.001 respectively. The WBC aggregation peak was at 1200 h and trough at 1600 h, the PSH peak was at midnight and the trough at 0400 h. WBC behaviour and FR status influence the flow properties of blood. The largest rise in WBC aggregation occurred from 0800 h to 1200 h; such an increase in aggregation could predispose to microcirculatory occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

A 40 year old man suffered eight years of vague but disabling symptoms, initially thought to be related to post viral fatigue syndrome, but ameliorated by the removal of a large atrial myxoma. The diagnosis of atrial myxoma is notoriously difficult, but should be excluded by echocardiography if there are predominant symptoms of progressive exertional dyspnoea, even in the absence of cardiological signs.

Clinical studies have demonstrated that patients with coronary artery disease (CAD) have markers suggestive of increased free radical (FR) activity when compared with normal subjects; however, the relationship between the extent of CAD and level of FR markers is not known. The following indices of FR activity, plasma malondialdehyde (MDA), plasma thiols (PSH), red blood cell (RBC) glutathione (GSH), and RBC superoxide dismutase (SOD) were measured in 58 patients admitted for coronary angiography and in 50 matched controls. Regression analysis demonstrated no significant correlation between MDA, PSH, GSH, or SOD, and the angiographic grade which indicated the severity of the CAD. Patients with angiographically proven CAD (median 7.9 nmol/ml IQR 6.9-9.2) and patients with a history suggestive of angina pectoris but normal coronary angiograms (median 8.4 nmol/ml IQR 7.4-9.9) had significantly raised MDA levels compared with the controls (median 6.85 nmol/ml IQR 6.1-7.4), p less than 0.001 and p less than 0.005, respectively. The patients with angiographically proven CAD had significantly lower GSH levels (median 1461 microM IQR 1348-1709, p less than 0.002) compared with the controls (median 1754 microM IQR 1492-1930). Significantly raised SOD levels also were detected in patients with angiographically proven CAD (median 121.8 U/ml RBC, IQR 113.8-143.9) and in patients with a history of suggestive of angina pectoris but normal coronary angiograms (median 146 U/ml RBC, IQR 96.8-156.7) when compared with controls (median 96.3 U/ml RBC, IQR 82.4-115.6), p less than 0.001 and p less than 0.02, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of atenolol on dipyridamole 201Tl myocardial perfusion tomography was evaluated in 12 patients with angiographically proven coronary artery disease. The patients had dipyridamole 201Tl tomography performed after 7 days treatment with 50 mg atenolol and then repeated after a further 7 days treatment with placebo. The images were interpreted qualitatively by two experienced observers and quantitatively using the Bullseye technique. Qualitative analysis of the images revealed that four of the 12 patients had larger defects on their scans whilst receiving atenolol compared to placebo. The remaining eight patients had defects which were the same size on both treatments. The severity of defects assessed qualitatively was not significantly influenced by atenolol therapy (P = 0.13, McNemera's test). The results obtained with the Bullseye method did not demonstrate significant statistical differences for defect size, degree of reversibility or percentage reversibility whilst the patients were receiving atenolol or placebo (Wilcoxon Rank Sum Test). Atenolol increased the size of perfusion defects on dipyridamole 201Tl tomography qualitatively and quantitatively for four patients in this group of 12 with proven coronary artery disease. Although this did not achieve a high level of statistical significance physicians should be aware that atenolol can influence the images obtained at dipyridamole 201Tl tomography.

Thirty eight relatives of a patient with Marfan syndrome were screened for the presence of this disorder. Marfan syndrome was newly diagnosed in living members of 4 generations in this family without evidence of ocular abnormality in any. After screening, 10 relatives were newly diagnosed as having definite, and 5 relatives as having possible, Marfan syndrome. Family screening has drawbacks as well as benefits for the patients. The main benefit is the identification and treatment of previously undiagnosed patients at risk of cardiac complications which are the major cause of mortality. The drawbacks include employment problems created for patients with Marfan syndrome as a direct consequence of our screening programme and the anxiety induced in previously asymptomatic family members who did not realize that they could be at risk. Also, the 4 adult patients with possible Marfan syndrome found it difficult to accept that a definite diagnosis could not be reached after they had been invited to attend a screening programme for a serious genetic disorder. This report illustrates the importance of screening all the relatives of a patient with Marfan syndrome to identify previously undiagnosed cases. However, before screening a family, the physician should be aware that a clear diagnosis may not be reached in all patients, and financial, psychological or social problems may arise as a result of the screening programme.

Optimal metabolic control during the first twelve hours after myocardial infarction may be associated with improved survival in diabetic subjects. A comparison of an intravenous insulin infusion regimen aimed at improving blood glucose levels (n = 35), with 'routine control' (n = 34) in the post infarction period has been carried out in diabetic subjects admitted to four Coronary Care Units over a two year period. However, glycaemic control was similar in both groups (intravenous infusion regimen, mean +/- SD capillary blood glucose 10.3 +/- 2.1 mmol/l, 'routine control' glucose 10.7 +/- 3.6 mmol/l). There were no differences in the rates of arrhythmias (31% v 32%), heart failure (46% v 47%) or mortality (17% v 18%). Mortality in diabetic subjects was lower than that quoted in previous studies but was higher than in non-diabetic subjects admitted to the Coronary Care Unit during the same period. Attempts to improve glycaemic control by means of intravenous insulin infusion were unsuccessful.

A 67-year-old woman had aortic and mitral annulus calcification resulting in severe stenosis and incompetence of the valves. Mitral annulus calcification produces specific echocardiographic abnormalities which may forewarn of technical difficulties during surgery.

Casein micelles of bovine skimmed milk were fractionated by permeation chromatography on porous glass (CPG-10, 50 nm followed by CPG-10, 300 nm) at 30 degrees C. Micelles were pooled in eight eluant fractions and their size distribution was determined by electron microscopy. The composition of casein in the eight fractions was determined by quantitative hydroxyapatite chromatography. Micelle size decreased progressively with increasing elution volume, and volume-to-surface average diameter ranged from 154 nm in fraction 1 to 62 nm in fraction 8. Concurrently there was a decrease in relative proportions of alpha s- and beta-caseins and a large enrichment of kappa-casein, which changed from 4.1% total casein in fraction 1 to 12.1% total casein in fraction 8. At least half the decrease in alpha s-casein proportions was attributed to the alpha s1-casein component, but the data also suggested a decline in proportions of alpha s2-casein in the smallest micelle fractions. A plot of kappa-casein fractional content versus micelle surface-to-volume ratio gave a straight line (correlation coefficient from linear regression 0.98) from which an average kappa-casein surface coverage of 1.5 m2/mg or 47.3 nm2/molecule was obtained. If a constant surface coverage for kappa-casein is assumed, the parameters of the linear equation predict that micelle voluminosity is inversely related to micelle diameter, being approximately 30% larger in fraction 8 compared to fraction 1.

Permeation chromatography on porous glass was carried out with skim milk at 20 or 30 degrees C using CPG-10 (50 nm) or a dual column system of CPG-10 (50 nm) followed by CPG-10 (300 nm). On columns of CPG-10 (50 nm) casein micelles were eluted at the void volume and were rapidly and efficiently resolved from non-micellar protein without micelle dissociation. The dual column system resulted in the additional resolution of the micelles into different size ranges. Examination of the resolved micelle fractions by electron microscopy showed a gradual decrease of weight average diameter (Dw) from 228.4 nm in the void volume fraction to 86.3 nm in the smallest micelle fraction. The translucent upper layer of a micelle sediment obtained by ultracentrifugation of skim milk at 30 degrees C consisted of casein aggregates intermediate in size between monomeric protein and the bulk micelle fraction as shown by its elution behaviour on CPG-10 (50 nm). These aggregates were enriched more than 2-fold with kappa-casein relative to skim milk, were devoid of alpha S2-casein and had an estimated value of Dw of 33 nm. The ultracentrifugate serum contained approximately 2.5% of total milk casein which had the elution characteristics of monomeric protein on CPG-10 (50 nm). It was concluded that the translucent sediment consisted of the smallest micelle fraction of skim milk and represented the minimum size range for casein polymerization in the natural milk environment. Overall, the results show that porous glass chromatography is an effective and convenient tool for the isolation and study of casein micelles.

Using 24-hour ambulatory electrocardiographic (ECG) monitoring, the incidence of cardiac dysrhythmias was investigated in 50 apparently healthy elderly subjects aged over 60 years. There was a high incidence of both ventricular and supraventricular ectopic beats, supraventricular tachycardia and sinus arrest. First- and second-degree block were also noted. The incidence of dysrhythmias bore no obvious relationship to age over 60, sex, blood presssure, cigarette smoking, caffeine and theophylline ingestion or resting 12-lead ECG abnormalities.

Fifty healthy, elderly subjects in whom a cardiovascular assessment, including 24-hour ambulatory electrocardiography had been performed, have been followed until death, or if surviving, for five years. Eight patients have died and 88 per cent of the survivors have had repeated 24-hour electrocardiography. Coronary death and the development of cardiovascular or neurological symptoms were not related to the presence in the original recording of significant dysrhythmias including frequent ventricular and supraventricular premature beats, R on T phenomena or sinus arrest. Treatment of these and other dysrhythmias in the asymptomatic elderly individual to prevent development of serious clinical sequelae is not justified.

We describe a case of amiodarone-induced thyrotoxicosis following heart valve replacement in a patient with a multinodular goitre. He responded to medical therapy with carbimazole and potassium perchlorate. Subsequent therapy with radio-iodine was followed 30 weeks later by the development of anaplastic thyroid carcinoma. It is possible that amiodarone caused a low uptake of radio-iodine by the thyroid. It is not known whether this possible low dose exposure to ionising radiation played a part in the development of the anaplastic carcinoma.

The clinical and bacteriological features of a case of endocarditis are described in which a Gram-positive coccus, presently designated Micrococcus sedentarius incertae sedis, was repeatedly isolated.

In Tayside region, from 1976 to 1986, the number of permanent pacemakers implanted per year more than doubled, with the increase particularly marked over the latter five years. In order to determine the factor(s) which had caused this increase in implantation rates, a retrospective analysis of patients undergoing pacemaker implantation during the period 1981-1986 was undertaken. No change in the number of elderly in the population, age of patients, mode of referral, waiting time before insertion or clinical indications for pacing was observed to account for this change. The advent of ambulatory ECG monitoring may have contributed to this increase, but the appointment of an extra cardiologist in Tayside in 1982 was believed to have been more important. These results suggest that the number of pacemakers implanted in a region is highly dependent on the number of cardiological staff in that region available for their insertion.

The subclavian vein has been used to implant permanent pacing catheters in 40 patients with symptomatic heart block. Though the cephalic and external jugular veins are usually preferred for this purpose in Britain, the use of these veins has certain disadvantages. In this study subclavian venepuncture by the infraclavicular approach was performed without diffculty and found to be a safe procedure. Three months after implantation, 7.5 per cent of patients had developed catheter tip dislocation and 87.5 per cent of patients were entirely free of complications.

Diabetes mellitus is associated with a high mortality after myocardial infarction. To see whether this may be decreased by improved diabetic control the effect of an insulin infusion regimen was studied in patients with acute myocardial infarction. From April 1982 to April 1983, 33 diabetics were admitted with acute myocardial infarction. Those being treated with diet alone or oral hypoglycaemic drugs continued with this unless control was poor, when they were changed to a "sliding scale" regimen of subcutaneous insulin injections thrice daily. Those already receiving insulin were maintained on thrice daily subcutaneous injections. From April 1983 to April 1984, 29 diabetics had acute myocardial infarction. Those receiving treatment with oral hypoglycaemic drugs or insulin were changed to continuous intravenous infusion of insulin, the aim being to maintain the blood glucose concentration at 4-7 mmol/I (72-126 mg/100 ml). Those being treated with diet alone continued with this if blood glucose concentrations were acceptable. Total mortality fell from 42% in the first year to 17% in the second (p less than 0.05). Over the same period mortality among non-diabetic patients with myocardial infarction did not change significantly. There was a significant fall in cardiac arrhythmias (expressed as the percentage of patients in whom arrhythmias were recorded) from 42% to 17% (p less than 0.05). The most significant fall in the incidence of complications occurred in those who had been receiving oral hypoglycaemic drugs on entry to the study (87% to 50%, p less than 0.05).

Vectorcardiograms and scalar electrocardiograms were recorded in 30 patients before and after aortocoronary saphenous vein bypass surgery to determine whether vectorcardiograms are helpful in making the diagnosis of perioperative transmural infarction. The vectorcardiogram indicated inferior infarction in 2 cases and anterior infarction in 1 case when the diagnosis was not apparent on the electrocardiogram. In the solitary case of anterior infarction diagnosed by the electrocardiogram, anterior infarction was already present on the preoperative vectorcardiogram. The study indicates that the recording of vectorcardiograms before and after aortocoronary bypass surgery facilitates the diagnosis of perioperative anterior and inferior infarction and may reveal perioperative infarction about a previously infarcted area.

Catheter tip dislocation is the main complication of permanent pacemaker implantation using the subclavian vein. In this study of 50 patients we compared the incidence of complications using two endocardial electrodes specially designed to prevent tip dislocation. One catheter had a helical endocardial electrode and the other had retractable nylon barbs. The helical electrode was superior in every respect and we recommend its use for pacing through the subclavian vein.

Prehospital coronary care involving a doctor and nurse team transported from the hospital by taxi has operated in Dundee for 18 months. Comparison of this service with the previous service shows it to be as effective, safe and relatively inexpensive.