[Penaly ordered care in France: principles of procedures and caregiver's role]. / Les soins ordonnés par la Justice en France : principes des procédures et place du médecin.

BACKGROUND: Penaly ordered care constitutes a type of legal penalty and a form of special care, linking health and legal environments, and as such is a difficult exercise for the various parties involved. METHODS: This article is based on a comprehensive study of medical and legal literature on the subject. RESULTS: Each of the measures presented has a legal basis, procedures for implementation and different application fields. According to the measure, the caregiver has a defined role in the organization of care and flexibility in dealing with specific legal authorities. Doctors are often uncertain of their rights and duties in this type of care. CONCLUSION: Penaly ordered care requires cooperation between two professional bodies with different ethical and professional requirements. Beyond this first difficulty, it appears that these measures are also complicated by the many pieces of legislation published recently, stressing the political will of the ever-expanding scope of ordered care, despite the lack of means downstream, sometimes to the detriment of their effectiveness.

Monohydroxylated fatty acid content in peripheral blood mononuclear cells and immune status of people at long times after the Chernobyl accident.

The monohydroxylated fatty acid content of peripheral blood mononuclear cells from 23 cleanup workers and 16 unexposed individuals was studied in relation to their immune status after the Chernobyl accident. Men with absorbed doses below 0.32 Gy showed higher levels of free and esterified 12-hydroxyeicosatetraenoic acid (12-HETE) than unexposed men, whereas 15-HETE and the 17-hydroxy derivative of C22 fatty acid (17-OH 22), either free or esterified in phospholipids, were increased in a dose-dependent manner. The percentage of CD4-positive cells was also increased significantly in heavily irradiated men, whereas the percentage of CD8-positive cells tended to decrease with dose. Furthermore, the absolute count of CD4-positive cells was correlated positively with the amount of esterified 15-HETE in the phospholipid fraction of the mononuclear cells and with the total 15-HETE. These results show for the first time that the accumulation of autoxidized/lipoxygenase products of polyunsaturated fatty acids in the mononuclear cells of irradiated individuals was associated with immune imbalance. This may be the basis for certain late effects of radiation such as autoimmune disorders, somatic and neoplastic diseases, and early aging.

Highly sensitive measurement of lipid molecular species from biological samples by fluorimetric detection coupled to high-performance liquid chromatography.

As the molecular species composition of glycerophospholipids provides more valuable information than the corresponding fatty acid composition, we have applied a fluorimetric detection (360 and 460 nm for excitation and emission wavelengths, respectively) of anthroyl derivatives of diradylglycerol species to minor phospholipid classes and subclasses from biological samples. Diacylglycerol species were obtained by phospholipase C treatment of phosphatidylcholine subclasses and phosphatidic acid extracted from rat thymocytes. Subpicomole measurements of molecular species from the minor subclass alkenylacylglycerophosphocholine could be achieved (e.g. 0.4 pmol of the 18:1/20:5 species). Such a sensitivity allowed study of the molecular species composition of another minor phospholipid, phosphatidic acid, and to evaluation of its alteration in mitogen-stimulated thymocytes as compared to unstimulated ones. Finally, we report that such a measurement is also applicable to other minor bioactive lipids with a hydroxyl group available, namely hydroxyeicosatetraenoates (HETEs), with a similar gain of sensitivity over conventional UV detection. Overall, these measurements, especially those of phospholipid molecular species, are sensitive, reliable and meaningful for precursor-product relationship between phospholipids.

Basal concentrations of free and esterified monohydroxylated fatty acids in human blood platelets.

Monohydroxylated fatty acids (HO-FA), namely 12-hydroxyeicosatetraenoic and 12-hydroxyheptadecatrienoic acids, are enzymatically formed in response to platelet activation. Different techniques, including gas chromatography (GC) and liquid chromatography-mass spectrometry (LC-MS), have been described to measure HO-FA in activated cells, but they are not well-adapted to resting cells. Measurements of free and esterified HO-FA at basal concentration require the prevention of platelet activation. For this purpose, such an activation was minimized by adding various inhibitors to the anticoagulant. Platelet recovery was greater in the protected group than in controls (473 x 10(9) +/- 4.0 x 10(9) platelets/L vs 410 x 10(9) +/- 4.53 x 10(9) platelets/L, respectively) (mean +/- SEM, n = 9, P < 0.05). Lipids were extracted and immediately hydrogenated to avoid fatty acid autoxidation occurring during the workup. Unesterified and esterified HO-FA were analyzed by GC-MS, and the former were lower in the protected group (1.52 +/- 0.84 pmol/10(9) platelets) than in the unprotected one (12.63 +/- 10.52 pmol/10(9) platelets) (mean +/- SEM, n = 9, P < 0.05). Interestingly, only traces of HO-FA were detected in both the triglyceride and sterol ester fractions, and they were also weakly esterified in phospholipids.

Contribution of phosphoinositides and phosphatidylcholines to the production of phosphatidic acid upon concanavalin A stimulation of rat thymocytes.

Stimulation of rat thymocytes by concanavalin A (Con A) results in a very early increase of the cellular level of phosphatidic acid (PA), while that of diacylglycerol (DAG) was not affected. As the biological activity of PA is very likely to be determined by its molecular species composition, the present study aims to investigate the pathways leading to the production of PA in Con A-stimulated rat thymocytes. Prelabeling the cells with [3H]arachidonic acid, [3H]myristic acid, [3H]choline, or [14C]lysophosphatidylcholine allowed us to determine that PA is formed by both phosphoinositide (PIs) and phosphatidylcholine (PC) hydrolysis. We then investigated whether PA derived from PC was formed by phospholipase C (PLC) or phospholipase D (PLD) hydrolysis. In the presence of 1-butanol, the production of phosphatidylbutanol was only observed in tetradecanoyl phorbol acetate (TPA)-stimulated cells. The use of a specific PC phospholipase C inhibitor resulted in a decrease of Con A-stimulated PA production in cells labeled with [3H]myristate. When cells were labeled with [3H]choline, only TPA stimulation induced a release of labeled choline. All together, these experiments suggest that PA is originated from two phospholipid sources, predominantly PI via PLC hydrolysis and to a lesser extent PC, by PLC hydrolysis also. Molecular species analyses by reverse phase HPLC are in agreement with this hypothesis, as diacyl-GP molecular species composition is similar to that of diacyl-GPC and DAG in resting cells, but resembles that of diacyl-GPI in Con A-treated cells. Thus, in stimulated cells, the amount of 18:0/20:4 species doubled while those of saturated and monounsaturated species decreased.

Platelet fatty acids and function in two distinct regions of Belgium: relationship to age and dietary habits.

We compared the dietary habits, fatty acid composition of plasma and platelet phospholipids, and platelet function in two groups of healthy Belgian male subjects, known to differ in their mortality rate from coronary heart disease (CHD). In the Walloon subjects, there was a larger intake of saturated and a lower intake of (n-6) polyunsaturated fats, confirmed by the fatty acid composition of plasma and platelet phospholipids. While plasma HDL and total cholesterol were similar in the present samples of the two communities, platelet aggregation to epinephrine was significantly higher in the Walloon subjects. When the two populations were divided into younger (28-54 years) and older (55-73 years) age groups, the older Walloon subjects exhibited platelet hyper-aggregability to most of the agonists, compared to the other three groups. In addition to dietary fats, alcohol and smoking habits, age was an important determinant of platelet phospholipid fatty acids and platelet reactivity. The present results reinforce those of previous studies, indicating that platelet behaviour is significantly affected by the main risk factors for CHD.

Nutrients, platelet function and composition in nine groups of French and British farmers.

In 260 male farmers (40-45 years) divided into 9 groups from different areas in France and Britain, coagulation, platelet aggregation, lipemia, fatty acids from plasma lipids and platelet phospholipids were determined in relation to the food intake evaluated by recall, weighing and chemical analysis of the diet. The clotting activity of platelets and their response to thrombin aggregation was significantly correlated on an individual basis with the intake of saturated fatty acids both in subsamples as well as in the whole study. Serum cholesterol was also significantly correlated with saturated fats but only on a group basis or on the totality of the study. Calcium, linolenic acid and alcohol in the diet were inversely related to certain platelet functions. Linoleic acid was inversely related to serum cholesterol and triglycerides. Dietary saturated fats were associated, with an increase in the platelet phospholipids not in saturated fatty acids but in 20:3 (n-9), known to promote platelet aggregation to thrombin, with a decrease in platelet cholesterol, also apparently regulating platelet functions. The present studies indicate that dietary saturated fats, calcium (hard water) and alcohol, influence platelet behaviour in a way strictly parallel to their known effect on coronary heart disease.

Influence of long-term diet modification on platelet function and composition in Moselle farmers.

Platelet function and composition, lipemia, and dietary habits were evaluated yearly in 98 male farmers from Moselle (East of France) before and after decreasing, in half of them, dietary saturated fats from 16.2% to 9.9% of calories (P/S from 0.32 to 0.97). One year after these dietary changes, cholesterol and triglycerides decreased by approximately 10%, platelet aggregation to thrombin by 81%, and their clotting activity by 30%. However, ADP aggregation was enhanced by 54%. At 2 yr the P/S was decreased to 0.7 and diet also modified in controls, with 18:2 being increased mostly in one group (P/S = 0.81) and 18:3 in another (P/S = 0.59). In both groups, the main platelet function tests were significantly depressed 1 yr later. Considering the whole study, the intake of saturated fat was mostly correlated (group and individual) with platelet aggregation to thrombin, platelet clotting activity, and 20:3 (n-9) in plasma and platelet lipids.

A sensitive method for the routine determination of plasma nicotine by flame ionization gas-liquid chromatography.

A gas chromatographic procedure for the analysis of nicotine in plasma, which uses quinoline as an internal standard, is reported. The nicotine is extracted with diethyl ether, concentrated without any evaporation, thus avoiding losses, and analyzed without derivatization. The recovery is 83.2 +/- 6.1% (n = 6). Although the analysis is carried out with a classical flame ionization detector, the detection limit is 0.1 ng/ml. Linearity is observed up to 100 ng/ml. The results of the precision analysis performed in the working range indicate a good reproducibility: a coefficient of variation of 5.2% is obtained for within-run analysis and 10.5 to 4.5% for nicotine values from 2.9 to 19.1 ng/ml for day analysis. Since a single run (the limitative step) lasts less than 15 min this improved procedure allows a great number of samples to be processed per day.

Platelet function after cigarette smoking in relation to nicotine and carbon monoxide.

In two sets of experiments involving 10 smokers, we followed the acute effect of inhaling smoke from cigarettes with five different nicotine yields (0.07 to 1.44 mg) on platelet function in relation to blood levels of carboxyhemoglobin and nicotine. Blood was drawn from fasted subjects who had not smoked for 10 hr before and after smoking one cigarette. Depending on the cigarette, the increase in platelet aggregation to thrombin, adenosine diphosphate, collagen, and epinephrine 10 min after smoking ranged from 0% to approximately 80% for the cigarettes with the higher nicotine yields. Blood nicotine levels increased from 112% to 644%. Clotting activity of platelet-rich plasma (PRP) and platelets rose by 16% with the cigarettes with the highest nicotine contents. Platelet activity correlated with blood nicotine levels but not with carboxyhemoglobin levels. Nicotine diluted in saline solution and added in vitro to PRP from six other subjects 2 min before the aggregation or clotting test at levels after smoking (10 and 20 ng/ml) induced a rise in platelet reactivity of the same order as that after smoking cigarettes. Data suggest that in some cigarettes, nornicotine and substances contained in tar may contribute to the effect of cigarette smoking on platelets.

Protective effects of dietary calcium and magnesium on platelet function and atherosclerosis in rabbits fed saturated fat.

Male rabbits were fed for 6 months a purified diet rich in fat (45% of calories), mostly saturated (butter) containing per 100 g either 354 mg of calcium and 46 mg of magnesium (group I), 948 mg of calcium and 46 mg of magnesium (group II), or 354 mg of calcium and 356 mg of magnesium (group III). In group II, fed the additional calcium, significant (P less than 0.001) changes were observed; i.e. prolongation of clotting time (platelet clotting activity), decrease in platelet aggregation to thrombin, and in the concentration of the plasma total cholesterol, with a less significant (P less than 0.05) decrease in plasma triglycerides. A significant (P less than 0.01) decrease in the ratio monoemes/18:2 in the plasma cholesterol esters but not in the plasma or platelet phospholipids was also found in these rabbits. In relation to their lower activity, platelets from group II exhibited a significant increase in 22:4n-6 (phospholipids) and in the ratio cholesterol/phospholipids, both significantly correlated with the platelet function tests. In this same group, the excretion of fecal lipids and saturated fatty acid 18:0 was increased by 4.3-fold and 7.6-fold, respectively. The severity of atherosclerosis and the accumulation of cholesterol in the aorta were significantly lower in group II, while the plasma level of calcium was similar to that of group I. In group III, fed additional magnesium, results were similar to those of group II, but less significant.

Comparative beneficial effects on platelet functions and atherosclerosis of dietary linoleic and gamma-linolenic acids in the rabbit.

Male rabbits (10 weeks old) were fed, for 20 weeks, purified diets rich in fat (45% of calories) containing saturated fats (butter), polyunsaturated fats (evening primrose oil + butter or sunflower oil + butter) for 20 weeks. Linoleic acid represented respectively 3.6, 33 and 34% of the dietary fatty acids, while gamma-linolenic acid was present (4.4%) solely in the second group. A significant increase in di-homo-gamma-linolenic acid in plasma, platelets and aorta was noted only in the animals fed evening primrose oil. Despite this, the results of the platelet aggregation to thrombin and ADP, the recalcification plasma-clotting time (platelet-rich plasma) and the severity of atherosclerosis were not significantly different from those observed in the group fed sunflower oil. In contrast, in comparison to the butter-fed animals, the two groups fed the polyunsaturated fats showed remarkable improvements in the clotting time (P less than 0.01) and in the severity of atherosclerotic lesions (evening primrose oil P less than 0.001; sunflower oil P less than 0.05). However, the response to thrombin-induced aggregation was significantly decreased (P less than 0.05) only in the evening primrose oil-fed animals. In these long-term studies in young rabbits, dietary gamma-linolenic acid did not seem to have marked beneficial effects, additional to those induced by linoleic acid, on platelet functions or on atherosclerosis.

Dietary fats and platelet function in French and Scottish farmers.

Although the intake of saturated facts still appears to be the environmental factor most closely associated with coronary heart disease (CHD), this does not necessarily mean that CHD is caused essentially or solely by blood lipids, as suggested by several investigators. It seems that blood platelets rather than (or at least in addition to) blood lipids might be the intermediate link between certain environmental factors (saturated fats, hard water) and CHD, through an effect on both thrombosis and atherosclerosis. Our recent studies in French and Scottish farmers, have shown that blood platelet function is more drastically affected by saturated fats than blood lipids. In those studies, platelet function was the only blood parameter correlated on an individual basis with the intake of saturated fat and inversely related to calcium intake. Calcium is probably the cation responsible for the protective effect of hard water against CHD in various countries. The results obtained also indicate that platelet function can be improved by increasing the intake of polyunsaturated fats at the expense of saturated fats. Finally, only platelet function was different from one region of France to another and from our region of Scotland to another; this difference could be related to the reported incidence of CHD in these various regions.

Platelet functions in relation to dietary fats in farmers from two regions of France.

To determine whether the long-term feeding of dietary fats affect platelet functions in man, platelet aggregation (to thrombin ADP, collagen, epinephrine) and clotting activity of platelet-rich plasma (PRP), platelet-poor plasma and of washed platelets were studied in a mobile-laboratory in 44 healthy male farmers (40--45 years) from two French regions Var and Moselle, in relation to lipemia, glycemia, dietary nutriments, and platelet phospholipid composition. In the Moselle subjects, the platelet clotting activity of PRP and of washed platelets, the platelet aggregation to thrombin and ADP, were highly significantly (p less than 0.001) increased as compared to those of Var, but not the plasma cholesterol, which was identical in the two regions. In Moselle, the intake of total calories, total lipids and saturated fats was higher than in the Var. However, it was only with the saturated fat intake (mostly stearic acid) that the platelet clotting activity (p less than 0.01) and the platelet aggregation (p less than 0.001) were highly significantly correlated. The platelet clotting activity was also significantly (p less than 0.001) correlated with the fatty acid composition of the platelet phospholipid fractions phosphatidyl serine + phosphatidyl inositol.