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Biomedical subjects

J L Beaumont

Publications and source records attributed to J L Beaumont.

At least 55 records · Page 3Linked to original sources

[Type II familial hyperlipoproteinaemia : value of plasma exchange treatment (author's transl)].

A 13-year-old boy with homozygous type II familial hyperlipoproteinaemia with marked cutaneous and tendinous xanthomatosis has been followed-up for a 3-year period. Signs of unstable angina developed at the age of 14 years, followed by the onset of a posterodiaphragmatic infarction at 16 years-ion. The usual poor spontaneous prognosis, and the lack of efficacy of medical treatment on blood cholesterol levels, led to suggest the use of plasmapheresis. Treatment was interrupted after three months in spite of its efficacy (blood cholesterol levels reduced by 36.2 p. 100 by the 3rd month); in fact, marked alterations in ventricular function, as shown by non-invasive exploratory tests, risked to provoke an ischaemic accident from hypovolaemia during plasma exchanges. This method is nevertheless the only one currently available that can appreciably lower cholesterolaemia levels in this affection. The treatment, which is not devoid of risks, should be undertaken during the early stages, before ventricular function deteriorates due to progression of atheroma.

Adolescent↗

Effects of probucol on the cholesterol content of skin in type II hyperlipoproteinemias.

500 mg of probucol were given twice a day for 6 months to 20 type II hyperlipoproteinemic patients, 14 men and 6 women, including 10 type IIb and 10 type IIa cases. Tendon xanthomas were present in 11 and xanthelasma in 4. Their mean blood cholesterol level was 435 +/- 100 mg/100 ml and triglycerides 210 +/- 138 mg/100 ml. A normal diet was maintained during the treatment period. Skin biopsies were made on the forearm, before and after the 6 month treatment. After lyophilization of the skin fragments, the free and esterified cholesterol contents were measured by gas chromatography after preparative thin layer chromatography on silica gel. The free and esterified cholesterol contents of the skin both appear to be significantly increased when the values found before treatment in these patients are compared with those of skin analysis in 10 normal controls: 2.25 to 1.58 micrograms/mg freeze-dried skin, p less than 0.001 for the esterified fraction. After 6 month probucol treatment the free cholesterol does not change significantly (2.25 to 2.16) and the esterified cholesterol increases (0.44 to 0.66, p less than 0.01). This effect is suggestive of an interaction of probucol with the synthesis and transport of cholesterol at the tissue level. It may be significant for the understanding of the effects of this drug and others on xanthelasma, tendon xanthomas, and atherosclerosis. In one of the cases studied here, the xanthelasma was greatly reduced during the treatment.

Cholesterol↗

[Vascular thrombosis in synthetic estrogen-progestogen users: an immune mechanism (author's transl)].

In a number of women the use of combined oral contraceptives (OC) may induce the production of anti-ethinylestradiol antibodies circulating as immune complexes (IC) and which precipitate when the serum is brought at 25% saturation in ammonium sulphate. Testing for tests ICs in 50 women who had never taken OCs, in 100 women on OCs but otherwise healthy, and in 17 women on OCs presenting with vascular thrombosis showed that 20% of all healthy women and more than 95% of women with thrombosis were immunoreactive. The statistically significant correlation found between thrombosis and the presence in the serum of ICs and anti-ethinylestradiol antibodies suggests that an immune mechanism might be responsible for the vascular lesions induced by oral contraceptives containing synthetic estrogens.

Adult↗

[Hypertriglyceridemia and tumors. Production of stable cultures of Green's lymphoma].

In Golden Hamster the Greene malignant lymphoma is a subcutaneous and homotransplantable tumor whose development is associated with a constant hypertriglyceridemia and a large-decreased plasma post-heparin lipase activity. The tumoral cell line is well maintained on a human fibroblast monolayer culture and is demonstrated to secrete two IgG immunoglobulins.

Animals↗

Vascular thrombosis and oral contraceptives - a risk correlated study.

An immunological mechanism of the vascular complications related to oral contraceptives (O.C.) was suggested by the demonstration of circulating anti-ethinylestradiol antibodies in several cases. According to the characteristics of the specific immunoglobulins (Ig), a test based upon Ig precipitability in 25% saturated ammonium sulfate was developed. This test was applied to several groups of women on O.C. with and without thrombosis, and to a control group. Results indicated: (1) that the test was positive in nearly 100% of women with a vascular thrombosis on O.C.; and (2) that the test could detect among healthy contraceptive users a group of women who may be considered as at risk. The role of adjuvant factors is considered.

Adult↗

Study of free and esterified cholesterol in skin in atherogenic hyperlipidemias.

Free and esterified cholesterol in the skin were assayed by gas chromatography after thin layer histochromatographic separation. There were 20 controls of both sexes, 36 subjects with type lla hyperlipoproteinemia, 27 with type IIb hyperlipoproteinemia and 19 with type IV hyperlipoproteinemia. Esterified skin cholesterol levels were higher in women with the type of lla disorder and in subjects with tendinous xanthomas. The levels of esterified skin cholesterol in type II women is not correlated with free skin cholesterol or with total circulating cholesterol; all these parameters are correlated in men. Furthermore, skin cholesterol levels were determined in 15 type II subjects before and after a six month treatment with the anticholesterolemic probucol. Cholesterolemia decreased 10 per cent, free skin cholesterol decreased slightly and esterified skin cholesterol increased significantly, as did the esterified/total skin cholesterol ratio. These data suggest the existence of a relationship between low vascular risk and elevated levels of esterified skin cholesterol (or elevated esterified/total skin cholesterol ratio).

Adult↗

[Detection of pill-induced antiethinylestradiol antibodies (author's transl)].

The synthetic hormones contained in contraceptive pills were shown to induce antiethinylestradiol (EE) antibodies in some women. These antibodies can be detected by the presence of circulating immune complexes (CIC) which are precipitated from serum in 25 p. cent saturated ammonium sulphate. A method of analysis of the anti-EE antibodies is described, in which binding of tritiated EE is measured with and without addition of unlabeled EE in excess. This method allows to identify specific reversible binding on saturable sites. Because of the large excess of non specific sites, the whole serum was enriched in antibodies before the binding measurement, either by previous separation of CIC, or by an affinity chromatography on a EE column. Results of this method confirmed the presence in a number of women on oral contraceptives, of immunoglobulins which were able to bind EE reversibly. The antibodies were found in CIC. in the absence of CIC, they were occasionally found in serum after an affinity chromatography on a EE column. This method is felt to allow a more accurate detection of women immunoreactive to the pill.

Antibodies↗

[Immunoglobulins and hyperlipoproteinemias].

With the objective of detecting autoimmune hyperlipidemias (AIH) we looked for the immunoglobulins bound to the low-density lipoproteins (test Ig-Lp): in 50 normolipidemic subjects and, in 133 hyperlipoproteinemic patients: 43 of type IIa, 34 of type IIb, 36 of type IV and 20 of Type V. The Ig-Lp was negative in the 50 normolipidemic subjects. It was positive in 26 hyperlipoproteinemic cases, including; 5 of type IIA, 3 of type IIb, 7 of type IV and 11 of type V. These results were compared to those of a previous smaller study, which had not been randomized. The present work confirms the interest of such a test. Although it does not allow to ascertain that the tested hyperlipoproteinemias are AIH, it suggests that there is a specific relation between immunoglobulins and lipoproteins.

Humans↗

[Free and esterified cholesterol of the skin in atherogenic hyperlipidemias].

Skin free and esterified cholesterol were assayed using gaseous chromatography following plaque histochromatography separation in 20 control, 36 patients with Type II a hyperlipoproteinemia, 27 with Type II b hyperlipoproteinemia and 19 with Type IV hyperlipoproteinemia. Skin esterified cholesterol was higher in females with Type II a hyperlipoproteinemia without or with xanthomatosis. But the skin esterified cholesterol level was not correlated with skin free cholesterol nor with blood total cholesterol levels, while in males these parameters were well correlated. On the other hand skin cholesterol was assayed in 15 patients with Type II hypercholesterolemia before and after a 6-month treatment with Probucol: there was 10p. 100 reduction of cholesterol level, and a weak decrease in skin free-cholesterol; in contrast, skin esterified cholesterol increased significantly as well as the skin esterified cholesterol/skin total cholesterol ratio (EC/TC). These data suggest a connection between weak vascular risk and skin esterified cholesterol high level (or high EC/TC in skin).

Aged↗

[Effects of probucol on skin cholesterol concentrations in patients with type II hyperlipoproteineamia (author's transl)].

Twenty patients (14 male and 6 female) with hyperlipoproteineamia (type IIa in 10 and type IIb in 10) were given probucol 500 mg b.d. during 6 months. Eleven patients had xanthoma tendinosum and 4 had xanthelasma. The mean plasma cholesterol and plasma triglyceride levels were 435 +/- 100 mg/dl and 210 +/- 138 mg/dl respectively. Normal diet was continued throughout. Skin biopsies were performed on the forearm before and after treatment. The skin fragments were freeze-dried, and free (FCh) and esterified (ECh) cholesterol concentrations were measured by gas chromatography after preliminary thin layer chromatography on silica gel. FCh and ECh were found to be significantly increased before treatment when compared with skin concentrations in 10 control subjects; FCh ranged from 2.25 to 1.58 microgram/mg (p < 0.001) and ECh from 0.44 to 0.16 microgram/mg of dry tissue (p < 0.001). After 6 months' treatment with probucol, there was no significant change in FCh (2.25 to 2.16 microgram/mg), but a significant rise was observed in ECh (0.44 to 0.66 microgram/mg; p < 0.01). This effect suggests that probucol interferes with cholesterol synthesis and transport in human tissues, which might help to comprehend the action of this and other drugs on xanthelasma, xanthoma tendinosum and atherosclerosis. In one of the patients, a xanthelasma was considerably reduced in size following probucol treatment.

Adult↗

[Treatment of prostatic cancer with diethylstilboestrol and detection of the vascular risk (author's transl)].

A retrospective study of immunologic behavior of patients suffering from cancer of the prostate and treated with oestrogens permits the proposal of the utilisation of a test that separates a high thromboembolic risk population due to oestrogens from a population that can benefit from this hormonotherapy. The so-called "oestrogen tolerance test" consists of seeking the presence of immune complexes by the method of precipitation of serum by 25% saturated ammonium sulphate. The group of patients where precipitates exceeds 700 micrograms/ml has a thrombo-embolic risk above 30% (41% in our series with serious complications such as pulmonary embolus and arterial thrombosis. The group of patients where precipitates are less than 300 micrograms/ml has a lower risk of arterial thrombosis (2,5%) and the observed accidents are benign. Finally, a test test when precipitate exceed 700 micrograms/ml should exclude diethylstilboestrol treatment.

Diethylstilbestrol↗

Purification of a monoclonal IgA with antiheparin activity.

A monoclonal IgA with antiheparin activity was obtained from a hyperlipidemic plasma. For the separation of the IgA antibody the plasma was passed through a column of Bio-Gel P-6 to eliminate the unbound heparin. As a second step, intervent dilution chromatography was used. The active peak of the intervent dilution chromatography was finally purified on heparin coupled to epoxy-activated sepharose 6B at pH 4.0. The obtained fraction gave a single arc with sodium dodecyl sulfate polyacrylamide gel electrophoresis. Using a lower pH (pH 2.8) for the separation, an aggregation of the IgA molecule was observed. Either the monomere or the aggregated IgA had a strong antiheparin activity. The presence of this antiheparin antibody is suggesting the possibility that certain immunoglobulins may play a role as heparin inhibitors in the development of hyperlipidemias.

Antibodies↗

Interaction between fibroblasts, lipoproteins and three antilipoproteins IgA kappa.

Human low density lipoproteins are metabolized by cultured human fibroblasts, through a specific metabolic pathway, which entails the regulation of intracellular cholesterol synthesis. When anti-lipoprotein IgA coming from patients with myeloma, mixed hyperlipidaemia and xanthomatosis were introduced into the system, we observed a decrease of the protein degradation of the LDL molecule, and a disappearance of the regulation of intracellular cholesterol synthesis. In the same system, an anti-lipoprotein IgA from a case of myeloma with mixed hyperlipidaemia, but without xanthomatosis, or control IgG and IgA were inactive and did not modify the LDL pathway.

Adult↗

Ethinylestradiol and diethylstilbestrol induced antibodies and vascular thrombosis.

Antiethinylestradiol antibodies were demonstrated in several oral contraceptive users. The antibodies could be precipitated from serum immune complexes by 25% saturated ammonium sulfate. This test of serum precipitation was applied to a comparative study of 116 women on O.C and 65 men treated with diethylstilbestrol for a prostatic cancer. Controls without hormones were included in each group. The test was shown to discriminate among the estrogen users reactive and unreactive persons. 34% of women and 41% of men had high levels of precipitated immunoglobulins in 25% saturated ammonium sulphate. Study of the specificity of the Igs purified from the precipitates in reactive cases, showed that they were binding ethinylestradiol with an affinity constant consistent with an antigen antibody reaction. It is concluded that the oral ingestion of two different synthetic estrogen compounds may induce antiestrogen antibodies. The relation of these antibodies with the increased incidence of vascular thrombosis is considered.

Adolescent↗