Anders Helgeland

EFFECT OF PROPRANOLOL AND PRAZOSIN ON BLOOD LIPIDS: The Oslo Study

In 23 hypertensive men, aged 47-55, propranolol reduced serum high-density-lipoprotein (HDL) cholesterol by 13% reduced the ratio of HDL to low-density-lipoprotein (LDL)+very-low-density-lipoprotein (VLDL) cholesterol by 15%, increased total triglycerides by 24%, and increased serum uric acid by 10%. Prazosin reduced total serum cholesterol by 9%, LDL+VLDL cholesterol by 10%, and total triglycerides by 16%. These changes are statistically highly significant. On combined treatment with propranolol and prazosin HDL cholesterol was still significantly reduced but changes in other blood lipids were small and insignificant. Uric acid remained elevated. When decisions about long-term therapy are made, such metabolic effects might be of special importance.

Evidence of increased peripheral catecholamine release in patients with long-standing, untreated essential hypertension

In 20 middle-aged men with untreated sustained essential hypertension for more than 5 years, both plasma adrenaline and noradrenaline were positively and significantly correlated with blood pressure. In both hypertensives and 19 normotensive control subjects supine arterial adrenaline concentrations were more than twice the venous concentrations consistent with adrenal production of this catecholamine. Adrenaline a--v(arterial-venous)differences(mean +/- SE) were significantly higher in the hypertensive group (82 +/- 15 pg/ml) than in the controls (50 +/- 5 pg/ml) indicating increased release of adrenaline in the hypertensives (P less than 0.05). Similarly, v-a(venous-arterial) differences of noradrenaline were significantly higher in the hypertensive (44 +/- 20 pg/ml) than in the control group (-10 +/- 16 pg/ml) indicating peripheral noradrenaline release in patients with essential hypertension. The findings are compatible with increased forearm noradrenaline and adrenal adrenaline release in these patients with long-standing untreated essential hypertension.

Serum triglycerides and serum uric acid in untreated and thiazide-treated patients with mild hypertension: The Oslo study

Levels of serum lipids, uric acid and body weight are reported from a controlled trial of drug treatment of middle-aged men with uncomplicated mild hypertension. The results come from 300 men after three years of follow up; 150 men in the treatment group and 150 men in the control group. The treatment has been standardized starting with hydrochlorothiazide alone and adding alpha methyldopa when necessary. In case of side effects, alpha methyldopa was replaced with propranolol. Pretreatment results demonstrated a strong covariation among body weight, uric acid and triglycerides. In the entire treatment group, there was no significant change in triglycerides after three years (increase from 1.85 to 2.02 mM/liter, P greater than 0.05). Cholesterol was also unchanged. Further analysis showed that certain patients reacted with an increase in triglycerides during treatment: those prone to a distinct increase in uric acid and those gaining weight. Those who needed combination therapy (having the highest pretreatment blood pressure) showed most of the increase in triglyceride and uric acid. In the group treated with hydrochlorothiazide alone, the triglycerides were unchanged. However, those selected from this group with a distinct increase in uric acid also showed an increase in triglycerides. The treatment increased the pretreatment positive correlation between uric acid and triglycerides.

ENALAPRIL, ATENOLOL, AND HYDROCHLOROTHIAZIDE IN MILD TO MODERATE HYPERTENSION: A Comparative Multicentre Study in General Practice in Norway

Enalapril, atenolol, and hydrochlorothiazide were compared in a double-blind randomised parallel study in general practice. 436 patients with mild to moderate hypertension were included at 76 centres. A two-week placebo run-in period was followed by 16 weeks of monotherapy. The initial doses were: enalapril 20 mg; atenolol 50 mg; and hydrochlorothiazide 25 mg. These were doubled if treatment was not effective after 4 weeks. Adverse reactions were the main reason for withdrawal from the study (9 on enalapril, 19 on atenolol, and 8 on hydrochlorothiazide). Systolic and diastolic blood pressures were significantly reduced in all three groups. The reduction in systolic blood pressure was greater on enalapril than on atenolol. Serum potassium was reduced and uric acid increased on hydrochlorothiazide. Fasting blood sugar rose on atenolol but fell on enalapril. The frequency of adverse reactions was acceptable in all three groups. After 16 weeks on treatment significantly more adverse reactions were recorded in the atenolol group than in the enalapril group. Enalapril is effective and well tolerated in patients with mild to moderate hypertension.

The Oslo study: Diet and antismoking advice. Additional results from a 5-year primary preventive trial in middle-aged men

In this randomized, primary prevention trial of 1,232 high-risk, middle-aged Oslo men, advice during 5 years about diet and smoking brought about a significant reduction (47%) in incidence of first major coronary heart disease (CHD) events in the intervention group compared with controls. Data are presented indicating that the net difference of 10% in serum cholesterol between groups was the main cause for this achievement and that the antismoking factor, due to a rather small net difference in quit rates (17 and 24% in control and intervention groups, respectively), contributed to a lesser degree. Analysis of social class reveals that the favorable results in the intervention group were present in all social strata, despite the unexpected finding that lower class men experienced a lower CHD incidence than men of higher socioeconomic status. Antismoking advice was especially effective in lower class intervention group men. Among cigarette quitters, lower social class men reduced their serum cholesterol more than higher social class men. However, for the total intervention group, higher status men had at least as great a reduction in serum cholesterol as did lower status men. With endpoint follow-up extended to 8.5-10 years, additional cases of CHD (nonfatal and fatal myocardial infarction and sudden death) numbered 7 and 10 in the intervention and control groups, respectively; CHD cases throughout the trial totaled 25 and 45 (P approximately equal to 0.02). Total deaths numbered 19 and 31, respectively (P approximately equal to 0.05).

Serum glucose levels during long-term observation of treated and untreated men with mild hypertension: The Oslo study

Serum glucose levels, triglyceride levels, and body weight are reported from a controlled drug trial in men, aged 40 to 49, with uncomplicated mild hypertension. The drug treatment started with hydrochlorothiazide alone, and methyldopa was added when necessary. If side effects occurred, methyldopa was replaced by propranolol. No detailed advice about diet, smoking, or weight reduction was given to any group. The untreated control subjects had a small increase in serum glucose levels during five years, from 6.08 to 6.21 mmol/liter. Those treated with hydrochlorothiazide alone and those treated with hydrochlorothiazide plus methyldopa had a small increase in serum glucose levels of the same order as that in the control subjects. However, those receiving the thiazide/propranolol combination experienced a sizeable increase in glucose levels, from 5.96 to 6.53 mmol/liter (p less than 0.001). This increase was significantly greater than the increase in the other groups (p less than 0.001). The thiazide/propranolol group also showed a significant increase in serum triglyceride levels (p less than 0.05). There was no difference in serum potassium levels in the different drug groups. The results indicate that moderate thiazide doses do not have significant effects on serum glucose levels in this age group. Propranolol in combination with thiazide seems to increase the level of serum glucose.

The Oslo study: CHD risk factors, socioeconomic influences, and intervention

This article reviews the methods and results of the large-scale, 10-year Oslo study. Two controlled intervention trials are described, one in healthy, normotensive men at high risk for coronary heart disease (CHD), the other in healthy men with mild hypertension. Cause-specific mortality is related to the major CHD risk parameters of serum cholesterol, cigarette smoking, and blood pressure and was found to be highest among the lowest socioeconomic class. Morbidity from myocardial infarction and total cardiovascular incidence decreased with lowered blood lipid levels and cessation of cigarette smoking in one trial. There was no difference, however, in total cardiovascular incidence as a result of antihypertensive therapy in the other trial. The effects on blood lipids of six commonly used single antihypertensive drug preparations and five combination preparations were examined. The study concluded that the beneficial lipid-lowering effect of the alpha-adrenergic blocker prazosin made it the antihypertensive drug of choice.

Coronary heart disease and treatment of hypertension. Some Oslo Study data.

The Oslo Hypertension Study began in 1972; patients were followed for an average of 66 months (range: 60 to 78). A total of 785 healthy men, aged 40 to 49, with mild hypertension was randomly assigned to either a drug-treated group or to an untreated control group. Hydrochlorothiazide was used alone in 36 percent of patients, in combination with propranolol in 26 percent, and with methyldopa in 20 percent. Other drugs, including combinations with hydrochlorothiazide, were used in 18 percent. A total of 95 percent of patients in the drug-treated group received hydrochlorothiazide. Complications of hypertension such as stroke and aneurysm occurred only in the control group. Coronary events were more numerous in the drug-treated group; thus, the total incidence of cardiovascular complications did not significantly differ between the treated and untreated groups. After five and 10 years, total mortality was the same in both groups. However, the coronary heart disease mortality rate at 10 years was significantly greater in the drug-treated group than in the untreated control group (14 versus three, p less than 0.01). This article presents possible reasons for the failure of antihypertensive drug therapy to prevent coronary heart disease. The adverse effect of diuretics and beta-adrenergic blockers, both on lipid and carbohydrate metabolism, is contrasted with the effect of the alpha-adrenergic blocker prazosin, which has been shown to have no adverse effect on the blood lipid profile. In a short-term trial that was part of the Oslo Study, prazosin was found to reduce total serum cholesterol by 9 percent, low-density lipoprotein and very-low-density lipoprotein cholesterol by 10 percent, and total triglycerides by 16 percent. All these changes are statistically significant.

Effect of Tonsillar Herniation on Cyclic CSF Flow Studied with Computational Flow Analysis

BACKGROUND AND PURPOSE: The Chiari I malformation, characterized by tonsils extending below the foramen magnum, has increased CSF velocities compared with those in healthy subjects. Measuring the effect of tonsillar herniation on CSF flow in humans is confounded by interindividual variation. The goal of this study was to determine the effect of herniated tonsils on flow velocity and pressure dynamics by using 3D computational models. MATERIALS AND METHODS: A previously described 3D mathematic model of the normal subarachnoid space was modified by extending the tonsils inferiorly. The chamber created was compared with the anatomy of the subarachnoid space. Pressures and velocities were calculated by CFA methods for sinusoidal flow of a Newtonian fluid. Results were displayed as 2D color-coded plots and 3D animations. Pressure gradients and flow velocities were compared with those in the normal model. Velocity distributions were also compared with those in clinical images of CSF flow. RESULTS: The model represented grossly the subarachnoid space of a patient with Chiari I malformation. Fluid flow patterns in the Chiari model were complex, with jets in some locations and stagnant flow in others. Flow jets, synchronous bidirectional flow, and pressure gradients were greater in the Chiari model than in the normal model. The distribution of flow velocities in the model corresponded well with those observed in clinical images of CSF flow in patients with Chiari I. CONCLUSIONS: Tonsillar herniation per se increases the pressure gradients and the complexity of flow patterns associated with oscillatory CSF flow.

High-Quality and Interactive Animations of 3D Time-Varying Vector Fields

In this paper, we present an interactive texture-based method for visualizing three-dimensional unsteady vector fields. The visualization method uses a sparse and global representation of the flow, such that it does not suffer from the same perceptual issues as is the case for visualizing dense representations. The animation is made by injecting a collection of particles evenly distributed throughout the physical domain. These particles are then tracked along their path lines. At each time step, these particles are used as seed points to generate field lines using any vector field such as the velocity field or vorticity field. In this way, the animation shows the advection of particles while each frame in the animation shows the instantaneous vector field. In order to maintain a coherent particle density and to avoid clustering as time passes, we have developed a novel particle advection strategy which produces approximately evenly-spaced field lines at each time step. To improve rendering performance, we decouple the rendering stage from the preceding stages of the visualization method. This allows interactive exploration of multiple fields simultaneously, which sets the stage for a more complete analysis of the flow field. The final display is rendered using texture-based direct volume rendering