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Abstract Objective Type III Hyperlipoproteinemia is a rare lipid disorder with a frequency of 1-5 in 5000. It is characterized by the accumulation of triglyceride rich lipoproteins and patients are at increased risk of developping atherosclerosis. Type III HLP is strongly associated with the homozygous presence of the ε2 allele of the APOE gene. However only about 10% of subjects with APOE2/2 genotype develop hyperlipidemia and it is therefore assumed that further genetic and environmental factors are necessary for the expression of disease. It has recently been shown that variation in the APOA5 gene is one of these co-factors. The aim of this study is to investigate the development of cerebrovascular atherosclerosis in patients with Type III hyperlipoproteinemia (Type III HLP) and the role of variation in the APOA5 gene as a risk factor. Methods 60 patients with type III hyperlipidemia and ApoE2/2 genotype were included in the study after informed consent. The presence of cerebrovascular atherosclerosis was investigated using B-mode ultra-sonography of the carotid artery. Serum lipid levels were measured by standard procedures. The APOE genotype and the 1131T > C and S19W SNPs in the APOA5 gene and the APOC3 sstI SNP were determined by restriction isotyping Allele frequencies were determined by gene counting and compared using Fisher's exact test. Continuous variables were compared using the Mann Whitney test. A p value of 0.05 or below was considered statistically significant. Analysis was performed using Statistica 7 software. Results The incidence of the APOA5 SNPs, -1131T > C and S19W and the APOC3 sstI SNP were determined as a potential risk modifier. After correction for conventional risk factors, the C allele of the 1131T > C SNP in the APOA5 gene was associated with an increased risk for the development of carotid plaque in patients with Type III HLP with an odds ratio of 3.69. Evaluation of the genotype distribution was compatible with an independent effect of APOA5. Conclusions The development of atherosclerosis in patients with Type III HLP is modulated by variation in the APOA5 gene.

One hundred and six patients with acute myocardial infarction admitted to hospital within four hours after the onset of symptoms were randomised to treatment with intravenous timolol (54 patients) or placebo (52 patients). Serum potassium concentrations were estimated at frequent intervals during the first 24 hours of admission. Patients in both treatment groups, who did not receive subsequent diuretic treatment, had a transient rise in serum potassium concentration, which was maximal after four hours. This rise was abolished by diuretic treatment in the placebo group but not in the timolol group, in which there was a pronounced and prolonged rise in serum potassium concentration. The change in serum potassium concentration in the first four hours after admission correlated with cumulative creatine kinase release in the placebo group, but not in the timolol group. Hypokalaemia (serum potassium concentration less than or equal to 3.5 mmol/l) occurred in 15 (28.8%) patients in the placebo group and in seven (13%) in the timolol group and was independent of infarct size. The frequency of hyperkalaemia was not increased in the timolol group. By increasing the serum potassium concentration and preventing hypokalaemia, the use of intravenous timolol early in acute myocardial infarction may have important clinical effects in addition to reducing infarct size. [ABSTRACT FROM PUBLISHER]

In a prospective study of 90 consecutive patients with acute myocardial infarction, 15 (28.3%) of 53 patients with an anterior wall infarction developed a left ventricular thrombosis diagnosed by cross sectional echocardiography. Patients received anticoagulants only after a left ventricular thrombosis had been diagnosed. Twenty eight patients had an inferior infarction, but none of these had a left ventricular thrombosis. Five (5.5%) of the 90 patients suffered a cerebrovascular accident, and all had an anterior wall infarction. In four of these five patients a left ventricular thrombosis was confirmed by echocardiography before the cerebrovascular accident. All patients with left ventricular thrombosis had apical akinesis. The incidence of a thrombosis did not differ in patients with a first anterior myocardial infarction and with reinfarctions. Among the 40 patients with a first anterior wall infarction, 12 with a thrombosis had a significantly higher incidence of enlarged heart on chest radiographs and significantly higher serum aspartate aminotransferase enzyme activity than those without. Thus patients with a large anterior wall infarction and with akinesis in the apical region are at high risk of developing a left ventricular thrombosis, which may be a source of peripheral emboli. Left ventricular thrombosis appears to be rare with infarctions in other locations. [ABSTRACT FROM PUBLISHER]

Serum potassium concentrations obtained on admission to hospital were inversely related to the incidence of ventricular fibrillation in 289 women and 785 men with acute myocardial infarction, 92 of whom developed ventricular fibrillation. Hypokalaemia (serum potassium concentration less than or equal to 3.5 mmol/l) was found in 122 patients (11.4%). The incidence of ventricular fibrillation was significantly greater in patients with hypokalaemia compared with those classified as normokalaemic (serum potassium concentration greater than or equal to 3.6 mmol/l) (17.2% v 7.4%). The increased risk of ventricular fibrillation in the hypokalaemic group was about the same for women and men. While they were in hospital patients with hypokalaemia developed ventricular fibrillation significantly earlier than did normokalaemic patients (median 0.3 hours v 7 hours). Hypokalaemia was more common in women (17.3%) than in men (9.2%), and 55% of the hypokalaemic patients had been treated with diuretics before admission compared with 22% of the normokalaemic group. Hypokalaemia on admission to hospital predicts an increased likelihood and early occurrence of ventricular fibrillation in patients with acute myocardial infarction. [ABSTRACT FROM PUBLISHER]

To examine the effect of short-term, high-dose anticoagulation on the subsequent occurrence of left ventricular (LV) thrombi after a first anterior wall acute myocardial infarction (AMI), 21 patients received placebo and 21 high-dose anticoagulants during the first 10 days of the acute infarction. They were studied with cross-sectional echocardiography 10 days and 1-3 and 6 months post infarction. At 1 month, 6 of 7 thrombi present in the placebo group at 10 days were still visible. No thrombi were detected at 10 days in the anticoagulation group, but 6 patients had developed a LV thrombus at 1 month. These 12 patients with LV thrombi were subsequently treated with oral warfarin for 2 months, after which all thrombi had disappeared. Warfarin was then discontinued, and a thrombus had recurred in 5 patients after 6 months. Apical akinesis at 10 days a predictor for thrombus with a sensitivity and specificity of 100% and 72.2% respectively.Three of the 13 patients with LV thrombi suffered stroke in contrast to none without thrombi (P=0.025).We conclude that after discontinuation of short-term high-dose anticoagulation therapy in anterior AMI, LV thrombi may develop rapidly and lead to embolic complications, particularly in patients with persisting apical akinesis. [ABSTRACT FROM PUBLISHER]

In a study of 1033 consecutive patients with acute myocardial infarction, serum potassium concentrations were determined on admission to hospital and studied with respect to the subsequent occurrence of atrial fibrillation and flutter and of ventricular tachycardia and fibrillation. The study cohort fulfilled the inclusion criteria for the Norwegian timolol trial in which they later took part. In multivariate analysis, with serum potassium concentrations as a continuous variable, age, the presence of ventricular tachycardia and fibrillation, and maximum level of aspartate aminotransferase greater than four times the upper limit of normal were significantly associated with the occurrence of atrial fibrillation and flutter, while serum potassium concentration was not. Serum potassium concentrations and time from onset of the infarction to hospital admission were significantly negatively associated with the occurrence of ventricular tachycardia and fibrillation; while age, cardiomegaly, transient hypotension, pathological Q-waves in the electrocardiogram, atrial fibrillation and flutter, and ventricular premature beats were positively related to these arrhythmias. [ABSTRACT FROM PUBLISHER]

Risk factors for systemic embolisation in patients with ventricular thrombi caused by an acute myocardial infarction were studied in 150 consecutive patients with an infarction of the anterior wall. Serial echocardiograms were performed 2-10 days after the acute event and patients were followed up for three months. Anticoagulation treatment was started only after the detection of thrombi. Of the 55 patients in whom a thrombus developed, 15 (27%) had peripheral emboli between 6-62 days; but only two (2%) of 95 patients without thrombus had emboli. Among 15 variables, the best single predictors of embolisation were age greater than 68 years (80% sensitive, 85% specific), pendulous thrombus (60%, 93%), and independent thrombus mobility (60%, 85%). Logistic regression analysis showed that a formula that included patient age, thrombus area, and the length of thrombus in the ventricular lumen predicted embolisation (sensitivity 87%, specificity 88%). There was no correlation between age and the thrombus variables. The risk of embolisation from left ventricular thrombi in acute anterior myocardial infarction can be accurately assessed from patient age and echocardiographic features. The risk of peripheral emboli is high in patients with left ventricular thrombi and those aged greater than 68. [ABSTRACT FROM PUBLISHER]

Acute inferior infarction often involves the right ventricle as well. For these patients, the prognosis is not as good as for patients with inferior infarction alone. Right ventricular infarction can be diagnosed with a high level of sensitivity and specificity by recording right precordial leads. We used V4R. 100 patients admitted to the Coronary Care Unit with an electrocardiographic diagnosis of inferior infarction were registrated consecutively. V4R was recorded in 95 patients; the right ventricle was affected in 35 of them. The mortality during the stay in hospital was 3% in the group with inferior infarction and 11% when the right ventricle was involved (p > 0.05). An unusually large proportion of the patients in both groups received thrombolytic therapy (more than 70%). The result may indicate that thrombolytic therapy is of particular benefit to patients with inferior infarction and involvement of the right ventricle.

We compared creatine kinase MB (CK-MB) mass and total creatine kinase (CK) sampled three times daily with conventional cardiac enzymes. The influence of the electrocardiogram (ECG) on admission, frequency of blood sampling, thrombolytic therapy, different upper reference limits of the biochemical markers and duration of symptoms were assessed in 100 consecutive patients with suspected AMI of whom 63 were confirmed according to WHO criteria. Early sensitivity but not specificity of CK-MB mass, with and without ECG, for cut points <8 microg/l was significantly better than total CK sampled frequently. The sensitivity of ECG on admission (52%) was significantly improved by CK-MB analysis (79%) but not by total CK. Duration of symptoms (range of means 3.5-9 h) or thrombolytic treatment had no influence on the sensitivity and specificity of CK-MB mass. In AMI with inconclusive ECG, CK-MB mass performed best of the markers with a sensitivity of 70% versus 17% of total CK (P<0.001) on admission. CK-MB mass was also elevated in 8 patients classified conventionally as unstable angina. We conclude that CK-MB mass is a more useful marker of AMI during the first 16 h of chest pain than frequently sampled total CK, ECG and conventional cardiac enzymes.

In the adult population, serum cholesterol level and risk of cardiovascular disease are related to some extent to habits and lifestyle established at an early age. We have estimated serum total cholesterol levels by means of a dry chemical method and have collected information on established cardiovascular risk factors among 1,203 young Norwegian men at conscription. 30 of the recruits with the highest serum cholesterol levels were later examined in the hospital's out-patient clinic. A total of 30.8% of the recruits were daily smokers. Mean serum total cholesterol was 4.05 mmol/l with a 97.5 percentile value of 6.31 mmol/l. The prevalence of coronary heart disease among parents was significantly higher among recruits from the upper cholesterol quintile (4.2%) compared with those in the lowest quintile (0.8%) (p = 0.02). These findings show that cholesterol screening at conscription is feasible and can be used to identify a group of men at high risk of subsequently developing cardiovascular disease.

Three days after the end of a bout of diarrhoea of 3 days' duration, a 19-year-old patient developed severe nocturnal thoracic pain unresponsive to isosorbitol dinitrate. There were no abnormal findings on physical examination, except a sweaty skin. SGOT (38 U/l), creatinine kinase (291 U/l, CK-MB 29 U/l) and lactate dehydrogenase (246 U/l) were all elevated. The ECG showed ST segment elevations in leads I, II, III, aVF and V1-V6 as well as negative terminal T waves in I, II, aVL, AVF and V3-V6, changes suggesting peri- and myocarditis. The Widal test gave a raised antibody titre (1:800) against Yersinia enterocolitica serotype O:3. Seven days later the immunoblot test demonstrated antibodies against the same organism, which was finally isolated from stool after 11 days. Treatment consisted of ciprofloxacin (500 mg twice daily for 14 days). All symptoms, as well as the biochemical and ECG abnormalities, quickly improved. The patient was discharged free of symptoms after 34 days.

To evaluate the influence of acute beta-blockade on the ability of predischarge exercise test data to predict long-term prognosis in patients admitted for suspected acute myocardial infarction, patients randomized at hospital admission to intravenous metoprolol or placebo were studied. Among 190 patients discharged alive, total 4-year mortality was 20.5% (n = 39); (33 cardiac deaths, 6 non-cardiac deaths). Non-fatal infarction rate was 6.8% (n = 13). Multiple logistic regression analysis revealed that total mortality and non-fatal infarctions were independently predicted by (a) inability to perform predischarge stress testing (event-free survival for patients exercise tested 79.5% vs 56.9% for patients not eligible for testing; relative risk (RR) 1.40, 95% confidence interval (CI) 1.10-1.78; P = 0.01), and (b) low predischarge exercise capacity (RR 1.44, CI 1.08-1.93; P = 0.034). ST segment shift > or = 1 mm did not predict mortality or reinfarction. Administration of metoprolol in the acute phase did not influence the predictive value of these parametres. It is concluded that assessment of exercise capacity at early exercise testing yields independent information for later death and myocardial infarctions, and that beta-blockade with metoprolol does not influence the predictive value of early exercise testing.

Patients admitted for suspected acute myocardial infarction within 6 hours (mean 3 hours 42 minutes) after onset of symptoms were randomised to double-blind treatment with low-dose oral aspirin or placebo. Early exercise ischemic responses, exercise capacity and resting left ventricular ejection fraction (radionuclide ventriculography) were estimated in 77 survivors 2-4 weeks later. Exercise performance and ejection fraction in patients with confirmed acute myocardial infarction were equal in the two groups. During exercise, patients treated with aspirin had significantly more silent ischemia (ST depression without chest pain) compared to placebo (28% versus 6%; P = 0.015). The occurrence of positive exercise tests (chest pain or ST-segment depression), however, was similar in the two groups. The results indicate that the administration of aspirin early after acute myocardial infarction increases the occurrence of silent ischemia but has no effect on left ventricular function.

Subtotal pancreatectomy in the rat was performed by a new method. Except for a small remnant along the splenal hilus, the gland was completely removed. Exocrine pancreatic insufficiency was confirmed by fat and nitrogen malabsorption. A moderate diabetes mellitus was seen. Insulin substitution or diet restriction was unnecessary. The absorption of vitamin B12 after oral administration of 10 ng 57CoB12 was 5.0 +/- 0.2 (ng 57CoB12 +/- S.E.M.) in unoperated rats and 5.1 +/- 0.1 in pancreatectomized rats (p greater than 0.5). Pancreatic extract (PE) (100 mg) increased the absorption of 57CoB12 in unoperated rats (p less than 0.01), but not in pancreatectomized rats (p greater than 0.2). PE (300 mg) reduced the absorption in unoperated rats (p less than 0.01). The results indicate that an optimal amount of pancreatic secretion may stimulate the absorption of vitamin B12.

Pancreatic extract (PE) contained small-molecular, thermo-stable as well as macro-molecular, thermo-labile factors capable of reducing the uptake of 57CoB12 bound to rat intrinsic factor by perfused rat intestinal segments (p less than 0.01 and p less than 0.01). Neither non-radioactive vitamin B12 nor non-pacreatic protein reduced the 57CoB12-uptake (p greater than 0.5 and p greater than 0.1) Crystalline trypsin and trypsinogen, but not chymotrypsin, also inhibited the uptake (p less than 0.05, p less than 0.02 and p greater than 0.05). The tryptic inhibition was abolished by soybean trypsin inhibitor (p greater than 0.05).

Fifty-three patients with a suspected first anterior wall acute myocardial infarction (AMI) were randomized to intervention with intravenous heparin followed by oral warfarin (26 patients) or matching placebo (27 patients). The regimen was started within 12 hours after the onset of AMI. Anticoagulation was maintained at a therapeutic level (for heparin, activated partial thromboplastin time 70 to 140 seconds; for warfarin, thrombotest 5 to 10%) for 10 days, and no bleeding episodes occurred. The baseline characteristics of the 2 study groups were well matched. In 7 patients in the placebo group and in none in the anticoagulant group, left ventricular thrombus developed during the study, as detected by serial 2-dimensional echocardiography. Early intervention with high-dose anticoagulant drugs may prevent the development of left ventricular thrombus in anterior wall AMI.

In a prospective study, 20 patients with a first acute myocardial infarction and no current treatment with diuretics or cardioactive drugs were randomized to treatment with intravenous timolol (10 patients) or placebo (10 patients). Plasma adrenaline, noradrenaline, and serum potassium were estimated at baseline (mean +/- SD 3.6 +/- 0.8 hours after the onset of the infarction) and 4 hours after the start of treatment. The patient selection criteria embraced a low-risk study population. Before treatment, the serum potassium concentrations correlated inversely with plasma adrenaline but not with plasma noradrenaline concentrations. A rise of serum potassium (mean +/- SD mmol/L) from 4.1 +/- 0.3 to 4.4 +/- 0.4 (p less than 0.05) in the placebo group and from 4.0 +/- 0.4 to 4.5 +/- 0.5 (p less than 0.05) in the timolol group was in multivariate analysis associated with infarct size, estimated as cumulative creatine kinase release, in the placebo group, and with the mean individual plasma adrenaline concentrations in the timolol group. By reversing the effect of adrenaline from a decrease to an increase in the serum potassium concentrations, timolol changes the relationships between circulating adrenaline, potassium, and infarct size.

Determination of vitamin-B12-binding capacity and gel filtration of human pancreatic juice (HPJ) and rat pancreatic juice (RPJ) demonstrated a vitamin B12 binder different from gastric intrinsic factor (IF). The results also indicated the presence of the pancreatic B12 binding in human duodenal juice. The binder in RPJ had no significant effect on the uptake of 57CoB12 and 57CoB12 bound to rat IF by perfused rat intestinal segments (p greater than 0.5; p greater than 0.1). The binder in HPJ had no effect on the uptake of unbound 57CoB12 or 57CoB12 bound to human IF by guinea pig intestinal brush borders (p greater than 0.05; p greater than 0.1). The results indicate that the pancreatic vitamin B12 binder does not influence the intestinal uptake of vitamin B12.