[Therapeutic education in primary cardiovascular prevention]. / Éducation thérapeutique en prévention primaire cardiovasculaire.

BACKGROUND: As primary prevention against cardiovascular diseases, Patient Therapeutic Education helps to develop a protective lifestyle within a socioeconomic context where risk factors abound. PATIENTS AND METHODS: Patient Therapeutic Education offers those eager to protect their cardiovascular health a program of six workshops. Upon enrolment, a Program aide conducts an educational diagnosis with the patient, specific to each workshop theme, so that he might understand the clinical, socio-professional, cognitive and psycho-affective dimensions. An evaluation of each workshop is requested from participants in the form of open and closed questions. RESULTS: The study comprised 2225people, majority women (79%), relatively old (age 63.9for women, 66.3for men), most often retired (65%). An analysis of the educational diagnosis notes a great frequency of classic risk factors; a good knowledge of the factors favoring them contrasting with the weak means implemented in everyday life to reduce their impact; the great majority of participants (68%) believe they have a well balanced diet; patients are greatly involved in their own health, with a slight external locus involving the general practitioner, the immediate entourage and society. The notes of the evaluation are usually maximum. CONCLUSION: Patient Therapeutic Education arouses strong interest in the public, allows a personalized approach that optimizes learning, increases knowledge and facilitates the use of new protective practices.

[Therapeutic education in primary cardiovascular prevention: 4 years sustained interest]. / Éducation thérapeutique en prévention primaire cardiovasculaire : intérêt prolongé à 4 ans.

BACKGROUND: Our patient therapeutic education program yields improvements in health after one year. But what can we see after 4 years, when the patient alone is responsible for following the program? PATIENTS AND METHODS: Two hundred and ninety-one patients participated in the first part of our study and were followed during one year. Four years into the ongoing study, we reviewed the progress of the first 200 patients. We compared the already published Risk Factors and Eating Habits scores between the beginning of the study (T0), one year later (T1) and after 4 years (T4). RESULTS: The Risk Factor score at T0 is 9.5±7.8, moving to 7±7.5 at T1, and then to 6.8±7.8 at T4 (P<0.001 between T0 and T1 and T0 and T4). Endurance physical activities saw the greatest improvement: 0.79±5 at T0, -1.07±4.5 at T1 and -1.61±4.5 at T4 (P<0.001 between T0 and T1 and T0 and T4). The Eating Habits score went from -18.2±7.3 to -22.2±6.4 and then to -23.5±6.4 (P<0.001 between T0 and T1 and T0 and T4). The best results were obtained through increased consumption of whole grains, green vegetables and fish. CONCLUSION: The positive results of the progress of risk factors and eating habits, noted after one year, are even greater four years after the end of the therapeutic education program.

Inflammation versus mechanical stretch biomarkers over time in acutely decompensated heart failure with reduced ejection fraction.

Heart failure can be associated with inflammation but it is unclear if inflammation is directly related to hemodynamic worsening or is an independent pathway. Our aim was to investigate inflammation and mechanical stress using serial measurements of biomarkers in acute and chronic heart failure with reduced ejection fraction (AHF and CHF). METHOD: The following biomarkers were measured on admission, at discharge and one month after discharge: B-type natriuretic peptide (BNP), high-sensitivity C-Reactive protein (hsCRP), Tumour Necrosis Factor alpha (TNFα), interleukin 6 (IL6), myeloperoxidase (MPO), suppression of tumorigenicity 2 (ST2), mid-regional pro-adrenomedullin (MR-proADM), galectin 3 (Gal3), Growth differentiating factor 15 (GDF15) and procalcitonin (PCT). RESULTS: In control CHF group (n=20, 69±11y, NYHA 1-2), most biomarker levels were low and stable over time. In AHF (n=55, 71±14y), BNP, ST2 and GDF15 levels were highly increased on admission and then decreased rapidly with clinical improvement; BNP, ST2 and GDF15 levels were statistically correlated (r=0.64, 0.46 and 0.39; p<0.001 for both). Both hsCRP, MPO, TNFα and Gal3 levels were increased in most AHF patients (70, 56, 83 and 98% respectively) with poor change over time. HsCRP, MPO and TNFα levels were correlated. IL6, MR-proADM and PCT levels were slightly increased, without change over time. Highest quartiles of BNP and ST2 were associated with death or readmission at one year (HR 2.33 [95CI 1.13-4.80] and 2.42 [1.27-4.60]). CONCLUSION: AHF is associated with systemic inflammation. This inflammatory response continued up to one month after discharge despite normalisation of mechanical stress-related markers.

[Therapeutic education in primary cardiovascular prevention. Interests and limits]. / Éducation thérapeutique en prévention primaire cardiovasculaire. Intérêts et limites.

GOAL OF THE STUDY: Lifestyle improvement is useful in the prevention of cardiovascular disease, but its practical implementation in the general population is limited. Patient therapeutic education can help go beyond these limits. PATIENTS AND METHODS: In primary prevention, we propose a personalized program including one or several individual and collective sessions to help the participants towards a healthier lifestyle. This includes better education about six risk factors (tobacco, sedentary lifestyle, overweight, high blood pressure, high cholesterol, diabetes) as well as advice on better eating habits. The first recommendation is to limit processed meats, the other recommendations advise more fish, green vegetables, whole grains and beans, and fruits. Scores are attributed to six risk factors and five eating habits. These scores are given at the time of the first session and again a year later, thus permitting time comparisons. RESULTS: For the first 291 participants in the program, we observed at one year a significant improvement in physical activities of endurance and in the consumption of the recommended food groups (fish, green vegetables, fruits, whole grains and beans). CONCLUSION: The patient's lifestyle has improved as a whole, certain parameters more than others. Assessed patient therapeutic education should be offered to a larger number of people.

[Cardiovascular disease prevention and life style modifications]. / Prévention des maladies cardiovasculaires et règles hygiéno-diététiques.

Cardiovascular diseases are mainly caused by atherosclerosis, the development of which is highly dependent on our Western lifestyle. Slowing this pathology depends on the reduction of risk factors such as hypercholesterolemia, high blood pressure, smoking, lack of physical activity, excess weight and diabetes. Drug treatment exists and is very effective, but too often they treat the immediate abnormality such as diabetes, high blood pressure and hypercholesterolemia and not the underlying causes: poor eating habits, lack of physical activity and excess weight. These have a negative impact on endothelial function, oxidative stress, and can trigger inflammation, arrythmias and thrombosis. Cardiovascular prevention must therefore target sedentary lifestyle, excess weight, and favor low-calorie, low-salt food and Mediterranean diet. The way this diet works begins to be understood and goes beyond simple cardiovascular prevention. Therapeutic education holds a growing and complementary role in the Public Health system which should call upon the strengths of all healthcare professionals.

Immune growth hormone (GH): localization of GH and GH mRNA in the bursa of Fabricius.

Expression of growth hormone (GH) and GH receptor (GHR) genes in the bursa of Fabricius of chickens suggests that it is an autocrine/paracrine site of GH production and action. The cellular localization of GH and GH mRNA within the bursa was the focus of this study. GH mRNA was expressed mainly in the cortex, comprised of lymphocyte progenitor cells, but was lacking in the medulla where lymphocytes mature. In contrast, more GH immunoreactivity (GH-IR) was present in the medulla than in the cortex. In non-stromal tissues, GH-IR and GH mRNA were primarily in lymphocytes, and also in macrophage-like cells and secretory dendritic cells. In stromal tissues, GH mRNA, GH and GHR were expressed in cells near the connective tissue (CT) between follicles and below the outer serosa. In contrast, GH (but not GH mRNA or GHR), was present in cells of the interfollicular epithelium (IFE), the follicle-associated epithelium (FAE) and the interstitial corticoepithelium. This mismatch may reflect dynamic temporal changes in GH translation. Co-expression of GHR-IR, GH-IR, GH mRNA and IgG was found in immature lymphoid cells near the cortex and in IgG-IR CT cells, suggesting an autocrine/paracrine role for bursal GH in B-cell differentiation.

Growth hormone and its receptor in projection neurons of the chick visual system: retinofugal and tectobulbar tracts.

Recent studies have shown the presence of growth hormone (GH) in the retinal ganglion cells (RGCs) of the neural retina in chick embryos at the end of the first trimester [embryonic day (E) 7] of the 21 day incubation period. In this study the presence of GH in fascicles of the optic fiber layer (OFL), formed by axons derived from the underlying RGCs, is shown. Immunoreactivity for GH is also traced through the optic nerve head, at the back of the eye, into the optic nerve, through the optic chiasm, into the optic tract and into the stratum opticum and the retinorecipient layer of the optic tectum, where the RGC axons synapse. The presence of GH immunoreactivity in the tectum occurs prior to synaptogenesis with RGC axons and thus reflects the local expression of the GH gene, especially as GH mRNA is also distributed within this tissue. The distribution of GH-immunoreactivity in the visual system of the E7 embryo is consistent with the distribution of the GH receptor (GHR), which is also expressed in the neural retina and tectum. The presence of a GH-responsive gene (GHRG-1) in these tissues also suggests that the visual system is not just a site of GH production but a site of GH action. These results support the possibility that GH acts as a local growth factor during early embryonic development of the visual system.

Expression, translation, and localization of a novel, small growth hormone variant.

A novel transcript of the GH gene has been identified in ocular tissues of chick embryos. It is, however, unknown whether this transcript (small chicken GH, scGH) is translated. This possibility was therefore assessed. The expression of scGH mRNA was confirmed by RT-PCR, using primers that amplified a 426-bp cDNA of its coding sequence. This cDNA was inserted into an expression plasmid to transfect HEK 293 cells, and its translation was shown by specific scGH immunoreactivity in extracts of these cells. This immunoreactivity was directed against the unique N terminus of scGH and was associated with a protein of 16 kDa, comparable with its predicted size. Most of the immunoreactivity detected was, however, associated with a 31-kDa moiety, suggesting scGH is normally dimerized. Neither protein was, however, present in media of the transfected HEK cells, consistent with scGH's lack of a signal sequence. Similar moieties of 16 and 31 kDa were also found in proteins extracted from ocular tissues (neural retina, pigmented epithelium, lens, cornea, choroid) of embryos, although they were not consistently present in vitreous humor. Specific scGH immunoreactivity was also detected in these tissues by immunocytochemistry but not in axons in the optic fiber layer or the optic nerve head, which were immunoreactive for full-length GH. In summary, we have established that scGH expression and translation occurs in ocular tissues of chick embryos, in which its localization in the neural retina and the optic nerve head is distinct from that of the full-length protein.

[Improvement of the prognosis of the acute coronary syndromes in Landes by lifestyle modifications]. / Amélioration du pronostic des syndromes coronaires aigus dans les Landes par la modification de l'hygiène de vie.

The global coverage of the patients having had an acute coronary syndrome requires the modification of their life hygiene. Six hundred and sixty-seven consecutive victims of this syndrome benefited from clinics by a nurse, aiming at decreasing their risk factors and to modify their food customs. The initial interrogation allows the collection of these items and every answer is transformed into a digital score. The patients being seen again every 6 months in consultation, progress was observed, not only for the control of the risk factors (the score passes from 6.4 to 5.1 P < 0.001) but also for that of the food customs (the score passes from 1.5 to 6, P < 0.001). The evolution of the patients was compared as they are (group 1, N = 216) or not (group 2, N = 448) followed regularly in consultation, on the basis of a voluntary service, with a follow-up of 20, 8 months. Three patients were lost sight. The patients of the group 1 have fewer cardiovascular events (17 patients with event vs 82, P < 0.02), in particular a cardiac insufficiency (2 vs 28, P < 0.01) or the other events bound to the atherosclerosis (13 vs 55, P < 0.02), They are less often hospitalised (14 vs 70, P < 0.001). The deaths are less frequent in group 1 (Curve of Kaplan-Meyer: P < 0.01; RR = 0.23; IC = 0.09-0.58. The bad hygiene of life, which led to the arisen of an acute coronary syndrome, can be corrected and this is translated by an improved prognosis.

Testicular growth hormone (GH): GH expression in spermatogonia and primary spermatocytes.

Growth hormone (GH) gene expression is not restricted to pituitary somatotrophs and has recently been demonstrated in a variety of extrapituitary sites in mammals and the domestic chicken. The possibility that GH gene expression occurs in the male reproductive system of chickens was therefore examined, since GH has established roles in male reproductive function and GH immunoreactivity is present in the chicken testis. Using RT-PCR and oligonucleotide primers for pituitary GH cDNA, GH mRNA was shown to be present in the testes and vas deferens of adult cockerels. Although testicular GH mRNA was of low abundance (not detectable by Northern blotting), a 690 bp fragment of the amplified testicular GH cDNA was cloned and had a nucleotide sequence 99.6% homologous with pituitary GH cDNA. GH mRNA was localized by in situ hybridization in spermatogonia and primary spermatocytes of the seminiferous tubules, but unlike testicular GH-immunoreactivity, GH mRNA was not present in secondary spermatocytes, spermatids or spermatozoa. The presence of Pit-1 mRNA in the male reproductive tract may indicate Pit-1 involvement in GH expression in these tissues. The presence of GH receptor mRNA in the testis and vas deferens also suggests they are target sites for GH action. These results demonstrate, for the first time, expression of the pituitary GH gene in the testis, in which GH mRNA was discretely localized in primary spermatocytes. The local expression of the GH gene in these cells suggests autocrine or paracrine actions of GH during spermatogenesis.

Ghrelin-induced GH secretion in domestic fowl in vivo and in vitro.

Although avian and mammalian species differ significantly in their regulation of GH secretion, preliminary studies have demonstrated in vivo GH responses to ghrelin in chickens, as in mammals. However, the relative potency of ghrelin as a GH-releasing hormone (GHRH) in birds is uncertain, as is its site of action. The intravenous administration of human ghrelin to immature chickens promptly increased the circulating GH concentration (within 10 min), although this was transitory and was only maintained for 20 min. This GH response was dose-related with an EC50 of approximately 3.0 microg/kg, comparable with the reported potency of human GHRH in chickens. When incubated with dispersed pituitary cells, human ghrelin induced dose-dependent GH release over a range of 10(-6) to 10(-9) M, with an EC50 of 7.0 x 10(-8) M, comparable with that induced by human GHRH (EC50 6.0 x 10(-8) M), although it was less effective at doses of 10(-6) to 10(-8) M. This was due to direct effects on pituitary somatotrophs, since human ghrelin increased GH release (determined by the reverse hemolytic plaque assay) from individual pituitary cells. The incubation of these cells with human ghrelin induced a dose-dependent increase in the numbers of somatotrophs secreting GH and in the amount of GH released by each cell. In summary, these results demonstrated that ghrelin is a dose-related GH-releasing factor in chickens with a potency comparable with that induced by human GHRH. The GH-releasing action of ghrelin is due, at least in part, to stimulatory actions on the numbers of somatotrophs induced to release GH and upon the amount of GH released from individual somatotrophs.

Extrapituitary GH in the chicken: underestimation of immunohistochemical staining by Carnoy's fixation.

GH has previously been shown to be present in peripheral extrapituitary tIssues of chick embryos, but the cellular distribution of GH immunoreactivity is still uncertain because of differing immunohistochemical findings. The possibility that this uncertainty reflects differences in fixation of the embryonic tIssues was assessed by comparing GH immunoreactivity in tIssues fixed in 4% (w/v) paraformaldehyde or Carnoy's fluid (60% ethanol (v/v); 30% chloroform (v/v); 10% acetic acid (v/v)). A widespread distribution of GH immunoreactivity was seen in paraformaldehyde-fixed tIssues, although it was particularly intense in the spinal cord, dorsal and ventral root ganglia, notochord, myotome, epidermis, crop, heart, lung and humerus. In marked contrast, GH immunoreactivity in embryonic tIssues fixed with Carnoy's was more discrete and mainly restricted to marginal and mantle layers of the spinal cord, spinal nerves, the ventral root ganglia and the extensor nerve of the anterior limb bud. Since these are neural derivatives, Carnoy's fixation appears to preferentially result in neural GH staining, whereas GH staining in neural and non-neural tIssues is seen after paraformaldehyde fixation. Carnoy's, because it is a precipitive fixative, may only fix large GH moieties, whereas GH in peripheral tIssues includes numerous molecular variants, many of which are of relatively small size. Paraformaldehyde, because it is a cross-linking fixative, preferentially fixes peptides and small proteins, and it may therefore fix more GH moieties than Carnoy's fluid. Carnoy's fixation appears to underestimate GH immunoreactivity in immunohistochemical studies on the cellular distribution of GH-like proteins in embryonic chicks.

Carbonic anhydrase inhibitors, interaction of boron derivatives with isozymes I and II: a new binding site for hydrophobic inhibitors at the entrance of the active site as shown by docking studies.

The interaction of human carbonic anhydrase (hCA) isozymes I and II with boron derivatives was investigated by kinetic and spectroscopic studies. These derivatives, tested as new inhibitors of carbonic anhydrase, are sulfonamide and non-sulfonamide boron derivatives and some of them proved to be moderately efficient inhibitors of hCA I and hCA II, their activities being comparable to those of the unsubstituted sulfonamides, the classical inhibitors of these zinc enzymes. Ph(2) BOH, one of the compounds with the highest affinity for hCA II in the present study, has been docked within the active site. After minimisation it was found situated at 7.9 A from zinc, within the hydrophobic half of the active site, in Van der Waals contacts with the amino acid residues: Val 121, Phe 130, Val 135, Leu 141, Val 143, Val 207 and Pro 201. This is the first time that a CA inhibitor has been found to bind at the edge of the active site cavity, similarly to the CA activator histamine, which binds on the hydrophilic half. This finding may be of importance also for the design of novel types of inhibitors with increased affinity for the different CA isozymes.

Carbonic anhydrase inhibitors: allylsulfonamide, styrene sulfonamide, N-allyl sulfonamides and some of their Si, Ge, and B derivatives.

Unsubstituted aromatic, heterocyclic and perfluoroalkylic sulfonamides possessing the general formula RSO2NH2 act as powerful inhibitors of the zinc enzyme carbonic anhydrase (CA). Unsaturated primary/substituted sulfonamides have never been investigated for their interaction with the enzyme. Here it is shown that such compounds, and more precisely allyl-sulfonamide and trans-styrene sulfonamide possessing the above general formula (with R=CH2=CH-CH2- and C6H5-CH=CH-, respectively) behave as nanomolar inhibitors of the physiologically relevant isozymes CAI and CAII. Some other derivatives of these two leads (incorporating Si(IV), Ge(IV) and B(III) moieties among others) were also synthesized and investigated for their interaction with CA, but showed decreased affinity for both isozymes. The structure-activity relationship for this class of CA inhibitors is discussed. Furthermore, it was observed that allylsulfonyl chloride is a strong CA inactivator, probably by reacting with amino acid residues critical for the catalytic cycle.

French multicenter trial of anistreplase versus heparin in acute myocardial infarction.

Eighty-four patients aged less than 71 years with less than 4-hour duration acute myocardial infarction (AMI) were randomized in a multicenter study to 30 U anistreplase or heparin (single injection of 6500 IU followed by 1000 IU/hr). Early reperfusion was assessed from ECG changes (50% of sum ST decrease 2 hours postdosing) and the CK release profile (CK peak less than 16 hours after onset of symptoms, CK slope greater than 10%/hr). Reperfusion rates in patients meeting at least two criteria of reperfusion were 62.5% on anistreplase versus 27.5% on heparin. On delayed angiogram (13.7 +/- 3.4 days), patency rates were 66% with anistreplase versus 47% (NS) with heparin in 76 patients. Global LVF was similar in both groups. With anistreplase, the mean lowest fibrinogen level was 0.43 +/- 0.55 g/l, plasminogen was 20 +/- 9%, and the highest F.D.P. was 1447 +/- 548 micrograms/ml. All values recovered by hour 48. In-hospital and 1-year follow-up mortality was 7.2% (three patients) with anistreplase versus 10.2% (four patients) with heparin. Bleeding occurred in 9.7% and 5.1% of the patients (NS), respectively. No intracranial hemorrhage occurred. Thus, with combined clinical criteria or reperfusion, anistreplase is twice as efficient as heparin, has a good tolerance, and is easy to use as a single injection.

Effects of dietary fats on the fluidity of human high-density lipoprotein: influence of the overall composition and phospholipid fatty acids.

The present study was undertaken to analyze whether the changes induced by dietary manipulations in the chemical composition of HDL, particularly in total phospholipids, phosphatidylcholine and sphingomyelin fatty acid composition, modified their fluidity. 12 healthy women, aged 26-49 years were studied. They consumed, over periods of 5 weeks, various isocaloric diets, each containing 30% of the calories as fat. 15.6% of the total calories were provided successively by olive oil, soybean oil, corn oil, and milk fats. The HDL fluorescence anisotropy was measured with 1,6-diphenyl-1,3,5-hexatriene (DPH) by fluorescence polarization. The HDL from the monounsaturated diet, olive oil, were the most fluid particles. The HDL fluorescence anisotropy was positively correlated with their free cholesterol percentage and negatively correlated with their triacylglycerol content and their triacylglycerol/phospholipid ratio. Moreover, the HDL fluorescence anisotropy was negatively correlated with the percentage of oleic acid in their total phospholipids and particularly in the phosphatidylcholine. These results suggest that the percentages of triacylglycerol and oleic acid in phospholipids of HDL have a fluidifying effect on these lipoproteins.

[The thyroid nodule. A retrospective study of 200 cases]. / Le nodule thyroïdien. Une étude rétrospective de 200 observations.

We analysed 200 cases of thyroid nodules collected in 2 units of the Laennec Hospital. The results of clinical examination, complementary investigations per and post-operative histology and medical follow up were analysed and compared with those in the literature. The malignancy rate was 18%. With the exception of 5 cases, a rigorous medical examination revealed at least one suspicious clinical sign in these patients. Thyroid isotope scan, which was cold in 82% of cases was of no value in distinguishing between benign and malignant nodules. The authors were not in agreement on the policy to be followed when faced with an isolated cold nodule. Fine needle aspiration is the only method which allows diagnosis but it is of low reliability. Ultrasound may be reassuring when it demonstrates fine walled, small diameter cysts only, but this situation is rare. We analysed the limits and pitfalls of these various methods. It is difficult to submit a patient to regular follow up for several years with antagonist treatment, where appropriate, and in addition malignant transformation may not be recognized. With knowledge of the good prognosis of cancers operated on at the microscopic intracapsular stage and the significant number of microscopic carcinomas discovered fortuitously in the course of surgery, it would appear reasonable to at least perform a cervicotomy with extemporaneous histological examination of any cold or isofixing nodule. Lobo-isthmectomy is in practice the solution adopted and its complications are rare and minimal.

Dietary fats and lecithin-cholesterol acyltransferase activity in healthy humans.

We analyzed the effects of different types of dietary fat on the lecithin-cholesterol acyltransferase (LCAT) activity in 20 healthy women aged 26-49 years, consuming 6-week diets containing 54% of the calories as carbohydrates, 16% as protein and 30% as fat. The tested fats were successively: low erucic acid rapeseed (LEAR oil), sunflower oil, peanut oil and milk fats (butter and cream). The fractional and molar rates of LCAT were higher after sunflower and peanut oil diets and decreased significantly after LEAR oil and milk fat diets. The LCAT activity was independent of the P/S ratio of the diet, but positively correlated with the percentage of linoleic acid in serum phospholipids and cholesteryl esters, and negatively correlated with the percentage of oleic acid in the same fractions. Our results showed no relation between LCAT activity and the concentration of plasma cholesterol or triglycerides, no change in serum cholesteryl ester/total cholesterol ratio and confirmed that the distribution of high density lipoprotein subfractions is due to prerequisites other than LCAT.

Seasonal variations of serum lipids and apoproteins.

Seasonal variations of blood lipids, which must be considered when performing long-term studies, could be partially due to dietary changes. In the present study, serum lipid parameters were measured each month for 1 year in nuns living in a monastery, whose diet was perfectly regular and controlled. The serum lipid variations observed consisted mainly of an increase in total cholesterol, low-density lipoproteins and apolipoprotein B in autumn and spring and an increase in high-density lipoprotein cholesterol in winter, whereas apolipoproteins A-I and A-II showed a marked increase in summer and at the beginning of autumn. These variations were probably induced by factors directly related to seasonal rhythm and not to dietary factors or physical exercise. Lastly, the influence of sex hormones seems to be very minor, as postmenopausal women (one-third of the persons) had an identical variation in their lipid parameters, to that observed in the whole group.