Anders G. Olsson

Prostaglandin E1 inhibits DNA synthesis in arterial smooth muscle cells stimulated with platelet-derived growth factor

The effect of prostaglandins (PG) on initiation of DNA synthesis in arterial smooth muscle cells (SMC) stimulated with platelet-derived growth factor (PDGF) was examined. A concentration of 10 ng/ml PGE1 inhibited DNA synthesis, measured as autoradiographically labeled nuclei, by about 70%. Similar results were obtained with PGE2 and PGD2 but at concentrations 10-20 times higher, whereas PGF2 alpha lacked effect. The inhibitory action of the prostaglandins was restricted to the first 6 h of the lag phase. Treatment with PGE1 also raised the intracellular concentration of cyclic AMP, indicating that the inhibition may be mediated via changes in the levels of cyclic nucleotides.

On the rise in low density and high density lipoproteins in response to the treatment of hypertriglyceridaemia in type IV and type V hyperlipoproteinaemias

In Type V hyperlipoproteinaemia the concentration of LDL and HDL cholesterol is low. When the hypertriglyceridaemia is normalized, either by diet or micotinic acid, both LDL and HDL increase. In Type IV hyperlipoproteinaemia both LDL and HDL cholesterol decrease with increasing VLDL levels. During treatment of Type IV the change in LDL cholesterol is linearly related to the pretreatment LDL concentration so that higher LDL levels will fall and the lower will rise. HDL levels will also rise. The fall in VLDL during treatment is rapid and the rise in LDL also occurs rapidly indicating a relationship between these two reciprocal changes. HDL cholesterol, however, however, remains constant some time after VLDL has reached its lowest level and the rise occurs later indicating another mechanism than for LDL. These changes in the three major lipoprotein classes deserve clinical attention. While both the fall in VLDL and the rise in HDL may be benefical from the point of view of atherosclerosis the rise in LDL may be harmful. These is at present no way to evaluate the effect of these complex changes. However, these findings stress the imporance of considering changes in lipoprotein levels and not only in total serum triglycerides and cholesterol during treatment of hyperlipoproteinaemia.

DOSE-RESPONSE STUDY OF BEZAFIBRATE ON SERUM LIPOPROTEIN CONCENTRATIONS IN HYPERLIPOPROTEINAEMIA

The effect of bezafibrate in the dosages 450, 900 and 1350 mg daily on serum lipoprotein concentrations were studied in 20 subjects with primary hyperlipoproteinaemia (16 of type IV, 2 of type II B, 1 of type III). Except for LDL cholesterol maximum effects were obtained with 450 mg daily. Total serum cholesterol and triglycerides (TG) fell significantly. Mean very low density lipoprotein (VLDL) TG fell by 54%. The maximum effect on low density lipoprotein was obtained with 900 mg daily. The effect was highly dependent on initial concentrations, decreases being observed above 4 mmoles/l and increases below that concentration. High density lipoprotein cholesterol increased by 31% (P less than 0.01) independently of the VLDL decrease. Three subjects suffered gastrointestinal side-effects on 1350 mg daily. Only benign reversible changes were noted on non-lipid measurements. Bezafibrate is a well-tolerated drug with a good VLDL TG lowering effect. It is particularly effective in increasing HDL cholesterol concentrations.

Effects of Hypolipidemic Regimes on Serum Lipoproteins

There is a rapid development in the area of serum lipid lowering regimes. Diets, drugs and other measures are used more and more frequently on more and more patients by more and more physicians. This increased use makes it mandatory that we know in detail the effects and the side-effects of these various regimes. One important aspect on the effects of the so called serum lipid lowering regimes is the effects on the different serum lipoprotein (LP) classes. Although it is well known that the serum lipids are bound to proteins and thus exist as LP in blood and that there are at least 3 major different LP classes we have surprisingly little knowledge about the effect of lipid lowering regimes on the concentration and composition of the LP classes. In fact it is not correct terminology to use expressions such as “lipid lowering drugs”, “cholesterol lowering drugs” or “triglyceride lowering drugs”. The correct terminology would be LP lowering drugs because it is not the serum cholesterol that is reduced by e.g. nicotinic acid but the concentration of the whole β (and also pre- β) lipoprotein molecules in serum (Carlson, 1969).

Effects of oxandrolone on plasma lipoproteins and the intravenous fat tolerance in man

Abstract Twenty-five patients with hyperlipoproteinaemia have been treated with oxandrolone 7.5 mg/day for 3 months. Plasma triglycerides (TG) were reduced from 4.12 to 2.87 mmol/1, whereas plasma cholesterol was 310 mg/100 ml before and 303 mg/100 ml during treatment. Analyses of the lipoprotein classes revealed that the plasma TG effect was the result of a reduction of TG in very low density (VLD) and high density (HD) lipoproteins. No TG change was seen in low density (LD) lipoproteins. Cholesterol was significantly reduced in VLD and LD lipoproteins, but as there was a significant increase in HD lipoproteins no net effect could be seen. During treatment hypo-α-lipoproteinaemia appeared in almost 50% of the patients. In 10 patients where the oxandrolone dose was increased to 10 mg/day a slight further reduction of plasma TG was seen, but cholesterol remained unchanged. The intravenous fat tolerance was significantly increased during oxandrolone treatment, suggesting that an increased removal of plasma TG could at least partly explain the effects of oxandrolone. In 60% of the patients serum transaminases increased and in one patient this rise was so pronounced that the drug was withdrawn. No subjective side effects were noted and no other changes of the laboratory control tests were found. It was suggested that oxandrolone alone may be useful in the treatment of patients with hypertriglyceridaemia. In hyperlipidaemias where plasma cholesterol is also increased oxandrolone should be considered only in combination with other drugs that are more efficient in lowering plasma cholesterol.

The effect of intravenous prostacyclin on resting pains and healing of ischaemic ulcers in peripheral artery disease

Prostacyclin (PGI2) was given intravenously in doses of 1 to 5 ng/kg/min to eight consecutive patients with end stage peripheral arteriosclerosis and ischaemic ulcers. Seven patients had intense ischaemic pains. Complete or partial healing of ulcers were seen in six cases (complete in three). In those whose ulcers healed (complete or partially) relief of ulcer pain was remarkable. Acute studies of the effect of prostacyclin on skin temperature of ischaemic areas showed no correlation with clinical effects. Seven patients had more or less pronounced subjective side effects, most often flushing, nausea, headache and uneasiness. As we previously have seen equally good healing and pain relieving effects by the administration of prostaglandin E1 without these side effects the latter compound is so far preferred in the treatment of severe peripheral artery disease. Controlled studies of the effect are needed.

Regression of Femoral Atherosclerosis in Humans: Methodological and Clinical Problems Associated with Studies of Femoral Atherosclerosis Development as Assessed by Angiograms

Ischemic heart disease is the most prevalent clinical consequence of atherosclerosis.1 Atherosclerotic peripheral artery disease is, however, one of the most frequent causes of disability in the middle-aged and elderly.2

Clinical and metabolic effects of pentaerythritol tetranicotinate in combination with cholesolvin or clofibrate

Summary Combined treatment of hyperlipidaemia with the nicotinic acid derivative pentaerythritol tetranicotinate (Perycit ® ) and clofibrate or the clofibrate analogue cholesolvin has been used in 26 ambulant patients with different types of hyperlipidaemia (types IIa, IIb and IV). The treatment started with Perycit ® 1g × 3 daily followed by cholesolvin 1 g × 2 or vice versa. The two drugs were then given together in the same doses as before and finally clofibrate was substituted for cholesolvin. The two types of drugs, Perycit ® and cholesolvin or clofibrate respectively, were found to have additive synergistic effects on plasma cholesterol as well as on plasma triglyceride concentration. There was no difference between cholesolvin and clofibrate in this respect. The usual side effects like flush were seen with Perycit ® , but the combined treatment with Perycit ® and cholesolvin or clofibrate produced no additional adverse reactions.

Impact of postoperative complications on the risk for chronic groin pain after open inguinal hernia repair

BACKGROUND Chronic pain is common after inguinal hernia repair and has become one of the most important outcome measures for this procedure. The purpose of this study was to determine whether or not there is a relationship between specific postoperative complications and risk for chronic pain after open inguinal hernia repair. METHODS A prospective cohort study was designed in which participants responded to the Inguinal Pain Questionnaire regarding postoperative groin pain 8 years after inguinal hernia repair. Responses to the questionnaire were matched with data from a previous study regarding reported postoperative complications after open inguinal hernia repair. Participants were recruited originally from the Swedish Hernia Register. Response rate was 82.4% (952/1,155). The primary outcome was chronic pain in the operated groin at follow‐up. Grading of pain was performed using the Inguinal Pain Questionnaire. RESULTS A total of 170 patients (17.9%) reported groin pain and 29 patients (3.0%) reported severe groin pain. The risk for developing chronic groin pain was greater in patients with severe pain in the preoperative or immediate postoperative period (odds ratio 2.09; 95% confidence interval 1.28–3.41). Risk for chronic pain decreased for every 1‐year increase in age at the time of operation (odds ratio 0.99, 95% confidence interval 0.98–1.00). CONCLUSION Both preoperative pain and pain in the immediate postoperative period are strong risk factors for chronic groin pain. Risk factor patterns should be considered before operative repair of presumed symptomatic inguinal hernias. The problem of postoperative pain must be addressed regarding both pre‐emptive and postoperative analgesia.

Concentration and chemical composition of plasma lipoprotein subfractions in patients with peripheral vascular disease. Evidence for normal apolipoprotein B but low cholesteryl ester content in small VLDL.

Subfractionation of the 3 major plasma lipoprotein classes was performed in 20 male patients with symptomatic peripheral vascular disease (PVD) and 18 male healthy controls of similar age and serum lipid levels as the patients in order to investigate if, at comparable levels of total serum lipids, any difference in the distribution or the chemical composition of the lipoprotein subfractions existed between patients and controls. Concentrations of free and esterified cholesterol, triglycerides, phospholipids, apolipoprotein B (apo B) and soluble apolipoproteins did not differ significantly in any lipoprotein subfraction of PVD patients compared to controls. Calculated molecular weights and numbers of lipoprotein particles/ml plasma were also similar in the 2 groups except that there were more heavy LDL particles in the patient group. Plotting concentrations of apo B against cholesteryl ester in the VLDL-D subfraction (Sf 20-100) yielded a linear regression in both groups. The PVD regression line was significantly steeper than that of controls. Calculation of the molecular mass of the various constituents of the VLDL-D fraction in the subjects with the highest content of esterified cholesterol in VLDL-D, where this difference was most pronounced, suggests that this difference was due entirely to a decreased number of cholesteryl ester molecules per lipoprotein particle in PVD. The findings suggest that a disordered metabolism of plasma cholesteryl esters may be present in certain PVD patients.