Changes in lipid and lipoprotein levels and Achilles tendon diameters and indices in familial hypercholesterolaemic patients with tendinous xanthomatosis treated by diet and bezafibrate for 2 years.

Thirteen young adult patients suffering from heterozygotic familial hypercholesterolaemia with tendinous xanthomatosis, previously treated with a suitable special diet, were studied to assess the effect of bezafibrate, given for 2 years at a dose of 800 mg/day, on plasma lipid and lipoprotein levels and on changes in size of the Achilles tendon xanthomas. Measurements were made before and at intervals during treatment, the tendinous xanthomas being measured by an echographic procedure to give data on antero-posterior and lateral diameters, thus enabling an Achilles tendon index to be defined. The results confirm the hypolipidaemic activity of bezafibrate, changes in the levels of total cholesterol, triglycerides, lipids and lipoproteins (LDL, VLDL and HDL) being similar in direction and magnitude to those reported previously. A significant regression in the size of the Achilles tendon xanthomas was observed in 11 of the 13 patients, and the regression in the Achilles tendon index correlated significantly with a favourable change in the ratio HDL/LDL + VLDL. It is suggested that, as a result of this objective observation, a favourable effect of bezafibrate treatment would possibly be seen on the anatomical atheromatous lesions which are usual in this type of hyperlipidaemia.

[Removal of low density lipoproteins on dextrans sulfate in 2 patients with familial monogenic hypercholesterolemia]. / Epuration des lipoprotéines de basse densité (LDL) sur sulfate de dextran chez deux patients affectés d'une hypercholestérolémie monogénique familiale.

Two patients-a 32 year old man with severe heterozygote familial hyperlipoproteinemia (FH) and a 9 years old girl with homozygote FH-were treated over eight months by LDL apheresis using dextran sulfate cellulose column (Liposorber, Kaneka, Japon). Plasma was separated from blood cells by filtration (TPE Cobe) or centrifugation (2,997 Cobe) through peripheral veins. An IV bolus of 10 IU/kg heparin was given together with local anti-coagulation with 55 g/l sodium citrate, 20 g/l citric acid at a ratio 1:25. Albumin supply was unnecessary. Plasma was removed every 2 weeks through liposorber LA 40 in the adult, and every week through liposorber LA 40 then 2 LA 15 in the child, mean plasma volume exchanged being 1.2 litres in the adult and 1.5 litres par session in the child. EFFECTIVENESS: the DSC column removed on the average 60 p. 100 of total cholesterol (TC) and 65 p. 100 of LDL.C. Apoproteins B levels were reduced by 58 p. 100. After each procedure there was a rapid increase in lipid levels to about the 80 to 90 p. 100 of pretreatment value. In the adult, we obtained levels of TC of less than 300 mg/dl with exchanges every 2 weeks combined with an HMG CoA reductase inhibitor (40 mg/day); in the child, with exchanges every week the same inhibitor did not permit a prolongation of the interval between 2 aphereses. SPECIFICITY: this was confirmed by elution of DSC column bound lipoproteins by 0.1 mol/l NaCl solution. However, the average removal of HDL.C and apoprotein A1 was respectively 31 p. 100 and 32 p. 100. Triglycerides levels were also reduced (48 p. 100). SAFETY: this was good in both cases. Using the filtration technic, hypotension was reported; this side effect did not appear with centrifugation. In the child, we observed immediate type reactions: nasal obstruction, headache and abdominal pain. The change in plasma protein concentration was caused by dilution and/or non specific absorption. CONCLUSION: LDL apheresis alone or combined with an HMG CoA reductase inhibitor is a safe technic, simple to manage without special equipment and producing marked LDL.C level reduction. However, there is also a reduction of HDL-C levels. Despite its high cost, it is a promising new approach to the treatment of FH.

[Effect on lipids, lipoproteins and apoproteins of labetalol prescribed in doses of 400 mg/day in hypertensive patients. Double-blind versus placebo study]. / Effet sur les lipides, lipoprotéines et apoprotéines du labétalol prescrit à la dose de 400 mg/j chez des patients hypertendus. Etude en double aveugle contre placebo.

The effects of labetalol on plasma lipoprotein metabolism were evaluated in a 3-month double-blind drug versus placebo study conducted on 30 consenting hypertensive patients, 15 of whom had normal plasma lipid levels and 15, minor type II hyperlipoproteinaemia; 20 patients received labetalol 400 mg/day and 10 the placebo. All patients remained in stable nutritional status throughout the study. Full clinical examination and blood sampling were carried out 30 days before, and on days 0, 30 and 90 of treatment. Whole blood was collected after 12 hours' fasting and immediately centrifuged prior to determination of plasma lipids (total cholesterol and triglycerides, by enzymatic assay), lipoprotein lipids (HDL, HDL2, HDL3, LDL, VLDL separated by ultracentrifugation in density gradient), apoproteins A1 and B (by laser immunonephelometry) and post-heparin lipoprotein lipase activity (PHLA). Significant changes in heart rate and systolic and diastolic blood pressures were noted in patients under labetalol but not in patients under placebo. Lipid and apolipoprotein levels were similar in both groups on day 0, and no significant variation in lipids, lipoprotein lipids and apolipoproteins were observed after 30 and 90 days of treatment with either labetalol or the placebo. At the end of treatment PHLA was unmodified in the group under placebo and raised in the group under labetalol (p = 0.05). The absence of changes in blood lipid values was found both in patients with normal lipidemia and in those with hyperlipidaemia. This study confirms that labetalol in doses of 400 mg/day has notable anti-hypertensive activity and, as previously reported and in contrast with other beta-blocking agents, is devoid of any adverse effect on lipid metabolism.

Comparative evaluation of the effects of ciprofibrate and fenofibrate on lipids, lipoproteins and apoproteins A and B.

In a double-blind study over a 3-month period, a daily dose of 100 mg ciprofibrate, prescribed in a single administration and a daily dose of 300 mg fenofibrate, prescribed in 3 administrations, significantly reduced the mean values of total cholesterol, LDL cholesterol and VLDL cholesterol, apoprotein B (P less than 0.001) and increased the mean values of HDL cholesterol (P less than 0.01) and total apoprotein A (P less than 0.05). The study, followed-up as an open trial using higher doses (100 or 200 mg/day ciprofibrate, 400 mg/day fenofibrate) tried to demonstrate clearly the benefit of therapy after 9 months with the 2 drugs and to establish the dose-response effects. Comparison of the 2 drugs at the optimal dosages, after 9 months of treatment, showed ciprofibrate to be more effective in increasing HDL cholesterol (P less than 0.05) and apo A (P less than 0.001). No other significant differences in terms of either therapeutic efficacy or biological tolerance became apparent between the 2 drugs. The results obtained in this comparative study were in accordance to those observed in separate trials for ciprofibrate or fenofibrate. Ciprofibrate has the benefit of a long half-life and may also be administered in the form of a single daily dose to patients suffering from major type II hyperlipoproteinaemia.

[Sea-blue histiocytes and storage diseases. 3 cases]. / Histiocytes bleu de mer et maladies de surcharge. Trois observations.

"Sea-blue" with prominent blue granules on Giemsa staining have been described in many diseases. The authors report three cases of storage diseases, in which these particular cells have been found. The significance and pathogenesis of "sea-blue" histiocytes are discussed.

[Lipids, lipoproteins, apoproteins and clinical arteriopathic manifestations]. / Lipides, lipoprotéines, apoprotéines et manifestations cliniques artériopathiques.

The authors present a historical review of the epidemiologic and pathophysiologic data which have supported the relations between the clinical complications of atherosclerosis on one hand, plasma lipids (cholesterol and triglycerides), lipoproteins (on electrophoretic basis), lipoproteins lipids (separated by ultracentrifugation or precipitation), and currently the plasma apolipoproteins on the other hand. The clinical applications of these data are considered.

[Xanthelasma palpebrarum and dyslipoproteinaemia: two retrospective studies (author's transl)]. / Xanthelasma et dyslipoprotéinémies: présentation de deux études rétrospectives.

In a retrospective study about 600 hyperlipoproteinaemic patients (390 men and 210 women, mean age 47), xanthelasma palpebrarum was infrequent (25 cases or 4.16 p. 100), since it was only at the third rank of chronic extra-vascular lipid deposits after arcus corneus and tendineous xanthomas. It was twice as frequent in men (5.12 p. 100) as in women (2.38 p. 100) and of regularly increasing occurrence until the sixth decade. Among the atherosclerotic risk factors, only obesity was significantly associated. The existence of atherosclerotic diseases was observed more frequently in patients with xanthelasma palpebrarum (40 p. 100) than in total hyperlipoproteinaemic population (28 p. 100). In a second retrospective study concerning 29 patients (15 men and 14 women, mean age 50), selected from the only presence of one or several xanthelasma palpebrarum, a lipoproteinaemic abnormality was observed in 27 cases (93 p. 100): 23 patients (71 p. 100) were hyperlipoproteinaemic (type IIa, IIb or IV) and in 4 out of 6 normolipidemic patients we observed an abnormal lipoprotein cholesterol distribution (LDL + VLDL cholesterol increase and HDL cholesterol decrease). In this group, we observed in nine patients (31 p. 100) unknown atherosclerotic diseases and tendineous xanthomas in other nine patients (31 p. 100).

[Fenofibrate: hypolipaemic activity and safety in long-term treatment. Effects on HDL, LDL, VLDL and apoprotein B in short-term treatment (author's transl)]. / Evaluation à long terme de l'activité hypolipidémiante et de la tolérance du fénofibrate. Effet à court terme du médicament sur les taux de lipides des lipoprotéines (HDL, LDL, VLDL) et apoprotéine B.

In a study started in 1973 and still in progress (1100 patient-years so far) fenofibrate in daily doses of 200-400 mg consistently proved effective, without any loss of activity with time. The drug lowered serum total cholesterol levels by 17-27% in type IIa, IIb and III primary hyperlipoproteinaemia (HLP) and serum triglyceride levels by 35-51% in type IIb and III HLP and by 46-54% in type IV HLP. Clinically and biologically fenofibrate was always well tolerated, even after 5 years' treatment. Side-effects were uncommon (4%) and mild, and they obliged to discontinue treatment in only 1% of the patients. Abnormal manifestations encountered during therapy appeared to be fortuitous. The effects of the drug on cardiovascular morbidity and mortality could not be determined from this trial. In a short-term study involving 21 patients with type IIa and IIb primary HLP, fenofibrate in doses of 200-400 mg/day produced a significant decrease in total cholesterol, LDL-cholesterol and apoprotein B. It is also reduced triglycerides and VLDL-triglycerides in type IIb HLP. The increase in HDL-cholesterol observed under fenofibrate was significant in type IIa HLP but not in type IIb HLP. In both types, there was a significant rise in HDL: LDL + VLDL ratio.

[Comparative effects of 17 beta-oestradiol and ethinyl-oestradiol on plasma triglycerides in female rats (author's transl)]. / Effets comparés de l'estradiol 17 beta et de l'éthinyl-estradiol sur la triglycéridémie.

Changes in plasma triglyceride levels were observed in female rats after castration and subsequent administration of incremental doses of 17 beta-oestradiol by injection or ethinyl-oestradiol orally. Castration significantly increased blood triglyceride levels and the dose of injected oestradiol which suppressed the effects of castration on vaginal smears and uterine weight also suppressed its effects on triglycerides. However, the oral dose of ethinyl-oestradiol which abolished the effects of castration on the genital tract further increased the levels of triglycerides. Differences in hepatic distribution of the two forms of oestrogen treatment may explain these discordant results.

[Comparative study of total cholesterol, HDL cholesterol, LDL + VLDL cholesterol. Two methods: precipitation by concanavalin A and ultra centrifugation (author's transl)]. / Etude comparative des taux de cholestérol HDL, cholestérol LDL + VLDL et du rapport cholestérol HDL/cholestérol LDL + VLDL dans trois populations par deux méthodes: précipitation par la concanavaline A et ultracentrifugation.

The authors determined in 3 populations (37 controls, 59 asymptomatic hyperlipemias, and 20 cases of arterial hyperlipemia) the total cholesterol, the HDL cholesterol and the LDL + VLDL cholesterol and their ratio by two methods : precipitation by concanavalin A and ultracentrifugation (AirFuge). These various lipid parameters were compared between 3 populations in order to determine their more or less discriminant character; furthermore, was established the degree of correlation between the results obtained by precipitation with concanavalin A and by ultracentrifugation. The results show : firstly, that the LDL + VLDL was significantly higher and the ratio HDL/LDL + VLDL significantly lower in hyperlipemia and in arterial disease compared with controls ; the HDL was significantly lower in arterial disease than in controls. No lipid parameter permitted one to differentiate between asymptomatic hyperlipemia and arterial disease. Furthermore, the correlation determined by the chi square method was very strong between the results obtained by precipitation with concanavalin A and ultracentrifugation as the coefficient of simple linear regression is very little different from the value + 1. They emphasize the interest of the method of precipitation by concanavalin A which is simple, rapid and very reliable.

[Quantitative analysis of lipoproteins in hyperlipoproteinemias of type IIa, IIb and IV (author's transl)]. / Analyse quantitative des lipoprotéines dans les hyperlipoprotéinémies de forme IIa, IIb et IV.

Cholesterol and triglyceride content of serum lipoprotein fractions isolated by ultracentrifugation have been studied in 33 healthy subjects and in 56 subjects affected by hyperlipoproteinemia of type IIa, IIb and IV. Patients with atherosclerotic disease were characterized by a general decrease of HDL cholesterol and by a negative correlation between HDL cholesterol and VLDL triglycerides; patients with type IIb and IV showed an increase of LDL lipoproteins. The increase of triglycerides in type IIb and IV was caused by elevation of VLDL triglycerides or LDL triglycerides, and the increase of cholesterol in type IIb is sometimes caused by elevation of VLDL cholesterol. It is evident that several subtypes exist within Fredrickson's classification. Patients with cerebral arterial disease when compared with patients affected by non-ischaemic disease, showed a negative and significant correlation between HDL cholesterol and total cholesterol.

The antiatheromatous action of silicon.

Silicon is a constituent of connective and elastic tissues. Administered intravenously or per os in rabbits, it inhibits experimental atheromas normally induced by an atheromatous diet, making atheromatous plaques much rarer and lipid deposits more superficial. Though the mechanism of silicon's antiatheromatous action remains shadowy, the impermeability's rise of the arterial wall is probably not the only influencing factor, because the arterial walls of animals under silicon do show a higher lipid concentration with respect to control animals. The preservation of the structure of elastic fibers, as well as of ground substance, and the absence of an increase in oleic acid in the aortic wall may also explain the rareness of atheromatous plaques.