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Biomedical subjects

C Théry

Publications and source records attributed to C Théry.

At least 19 recordsLinked to original sources

Comparative efficacy of the intravenous administration of linsidomine, a direct nitric oxide donor, and isosorbide dinitrate in severe unstable angina. A French multicentre study. French Group of Investigators.

AIMS: Although linsidomine shares common properties with nitrovasodilators, it releases nitric oxide directly without catalytic involvement by thiols. We conducted a prospective, randomized, multicentre, parallel group, single-blind study to compare the efficacy of intravenous administration of linsidomine with that of isosorbide dinitrate in unstable angina. METHODS AND RESULTS: Between November 1990 and July 1992, 568 patients with suspected unstable angina (class IIIB of the Braunwald classification) received a continuous infusion of either linsidomine (1 mg.h-1 on average) or isosorbide dinitrate (2.5 mg.h-1 on average) for 72 h. All patients received concomitant aspirin and intravenous heparin, 81% beta-blockers and 38% calcium antagonists. Holter monitoring was performed in all patients and analysed blindly. Only 25% of the patients had at least one episode of chest pain during the study (24.6% vs 25.8% in the linsidomine and isosorbide dinitrate groups, P = 0.74), of which 12% were associated with ECG changes. Holter criteria yielded similar results in both groups: 33% of patients presented episodes of myocardial ischaemia (32.6% vs 33.9% in the linsidomine and isosorbide dinitrate groups, P = 0.74), while 45% showed episodes of ventricular arrhythmia (43.5% vs 46.5% in the linsidomine and isosorbide dinitrate groups, P = 0.48). The incidence of serious clinical events at 72 h (death, myocardial infarction or myocardial revascularization) was 6.5% (5% vs 8% in the linsidomine and isosorbide dinitrate groups, P = 0.17). CONCLUSION: Intravenous linsidomine is at least as efficacious as isosorbide dinitrate in the stabilization of patients with severe unstable angina.

Aged

[Current status of treatment of chronic cardiac insufficiency].

When there is no correctable cause, cardiac failure continues to progress and outcome is poor. However several controlled clinical trials have shown that several therapeutic agents relieve symptoms, improve exercise tolerance and, for some, reduce mortality. Patients in NYHA functional class II, III and IV, whose systolic function is impaired should be treated by digitalis, diuretics and angiotensin-converting-enzyme inhibitors. These therapeutic agents are complementary and each of them are required. Moreover a study has shown that the impairment of patients in NYHA functional class I (who are still asymptomatic but with a ventricular ejection fraction < 35%) could be slowed by angiotensin-converting-enzyme inhibitors. In each case, it is of paramount importance to exclude treatable causes of heart failure because the best the symptomatic treatment can do is slow the inevitable worsening of the disease.

Angiotensin-Converting Enzyme Inhibitors

Involvement of Livertine, a hepatocyte growth factor family member, in neural morphogenesis.

The formulation of the nervous system in vertebrate embryos involves extensive morphogenetic movements that include the folding of the neural tube and the migration of neural crest cells. Changes in cell shape and cell movements underlie neural morphogenesis but the molecular mechanisms involved in these processes in vivo are not well understood. Here, we show that a new member of the hepatocyte growth factor family, which we name Livertine, is expressed in frog embryos in neural cells including neural crest and midline neural plate cells which are undergoing pronounced morphogenetic movements. The ectopic expression of Livertine perturbs gastrulation and leads to positional changes in injected cells without apparently changing cell type. These results suggest that one of the normal functions of Livertine is the control of neural morphogenesis in the vertebrate embryo.

Amino Acid Sequence

Homozygous variant of antithrombin with lack of affinity for heparin: management of severe thrombotic complications associated with intrauterine fetal demise.

Patients with homozygous heparin-binding-site (HBS) qualitative antithrombin deficiencies are at significant risk of venous and arterial thrombosis. We report on the eighth case of homozygous HBS deficiency, and the fourth case concerning the Arg 47-Cys mutation. The proposita is a 25 year old, without known thrombotic antecedent, despite an oral contraceptive therapy for 7 years. After 25 weeks of a first pregnancy, she presented an intrauterine fetal demise complicated with deep vein thrombosis and pulmonary embolism. Heparin therapy was inefficient (no clinical nor angiographic improvement, no biological hypocoagulability). Heparin cofactor activity was < 10%, antigen concentration was normal. The crossed immunoelectrophoresis of patient's plasma, with and without heparin, showed a typical profile of qualitative HBS antithrombin deficiency. The molecular analysis revealed an homozygous Arg 4-Cys mutation. Antithrombotic therapy was achieved with continuous infusion of antithrombin concentrates (80 IU/kg/day) and unfractionated heparin (500 IU/kg/day) during 12 days, leading to clinical improvement, and followed by treatment with vitamin K antagonists. This observation emphasizes the risk of intrauterine fetal demise and the inefficiency of heparin therapy without antithrombin infusion in type II HBS homozygous deficiency. The management of a future pregnancy will probably require repeated infusions of antithrombin.

Adult

Roles of kringle domain-containing serine proteases in epithelial-mesenchymal transitions during embryonic development.

Transformation of an epithelial sheet into a migrating mesenchymal cell population implies the destruction of the basal lamina underlying the epithelium, and the subsequent localized digestion of the extracellular matrix by the migrating cells. Proteases are involved in these processes. Among them, molecules containing both a serine protease domain and at least one kringle domain have been identified as possible important effectors. Interestingly, related proteins containing an inactive serine protease domain also seem to play a role, suggesting that the function of these molecules in epithelial-mesenchymal transformation is not confined to proteolytic digestion of cell attachments. Instead, these molecules act through specific tyrosine kinase receptors in the membrane of the responding cells. In this review, we summarize data implicating this family of molecules in various epithelial-mesenchymal transitions during embryonic development. Our major focus of attention are: hepatocyte growth factor/scatter factor (HGF/SF), its tyrosine kinase receptor proto-oncogene c-met, and the related peptide factor HGF-like/macrophage-stimulating protein (HGF1/MSP), whose receptor is the Ron tyrosine kinase. c-met and Ron also have another close homolog in the chick, called Sea, whose ligand remains unknown. Interestingly, HGF/SF is activated by other plasminogen-related molecules which, apart from a specific activator, include the protease urokinase. HGF/SF, c-met and HGF/MSP are expressed in dynamic ways during early embryonic development, correlating with regions undergoing epithelial/mesenchymal transformations. Moreover, several assays are now starting to reveal great pleiotropism of function during development, including both the loss and the acquisition of epithelial morphology according to the cell type and assay used, as well as angiogenesis, kidney tubule morphogenesis, cell motility, the maintenance of competence for neural induction and some aspects of the later development of the musculoskeletal and nervous systems.

Animals

[Aortitis in Horton disease. Review of the literature].

First described in 1937, giant cell aortitis (aortitis associated with giant cell arteritis) occurs in 20 to 40% of patients with giant cell arteritis and is often clinically silent. Temporal involvement usually precedes aortic involvement. The process may involve the entire aorta, but complications are usually related to thoracic involvement. Patients with giant cell aortitis may be asymptomatic, or present with aortic arch syndrome, dilation of the aorta, aortic aneurysm, aortic dissection, sudden rupture of the aorta, or aortic valve incompetence. Thoracic aneurysms are usually fusiform and can be complicated by dissection in up to 50% of patients. Aortic involvement may be the presenting feature of giant cell arteritis: it may also occur in patients with preexisting temporal arteritis, often when corticosteroid therapy is reduced or discontinued. Aortic rupture complicating aortitis may be the cause of death in 3-12% of patients with giant cell arteritis. Clinical follow-up with assessment of disease activity by chest X-ray and biological markers of inflammation should be performed yearly in giant cell arteritis. Aortic involvement should be suspected if cardiac or vascular echo-Doppler shows evidence of an aortic arch syndrome, aortic dilation, aneurysm, or of aortic valve incompetence. Corticosteroid therapy, beginning with a dose of 1 mg/kg/day remains the key point of therapy. The dose is subsequently adjusted based on the clinical course and the results of ancillary tests. This treatment might prevent fatal outcome with aortic rupture. Long-term follow-up of all patients with giant cell arteritis or polymyalgia rheumatica is essential, as complications may develop late in the course of the disease.

Aortitis

Expression of HGF/SF, HGF1/MSP, and c-met suggests new functions during early chick development.

We report the cloning of fulllength cDNAs for a plasminogen-related growth factor, hepatocyte growth factor/scatter factor (HGF/SF), its tyrosine kinase receptor, c-met, and a close member of the same family, hepatocyte growth factor-like/macrophage stimulating protein (HGF1/MSP), from the chick. We have used these cDNAs to provide the first report of the expression of this family of growth factors and the c-met receptor at early stages of vertebrate development. RNAase protection and wholemount in situ hybridization were used on chick embryos between formation of the primitive streak and early organogenesis. We find patterns of expression for HGF/SF and its receptor c-met consistent with their known roles in epithelial-mesenchymal transformation and angiogenesis. In addition, these genes and HGF1/MSP are expressed in discrete locations within developing somites, suggesting a role in paraxial mesodermal development. Very strong and early expression of HGF/SF in the elevating limb buds suggests its involvement in limb outgrowth. HGF1/MSP is expressed in the notochord and then in the prospective floor plate region and could play a role in development of the neural tube. Interestingly, c-met is often more closely associated with HGF1/MSP than with its known ligand, HGF/SF, raising the possibility that c-met expression may be induced by HGF1/MSP.

Amino Acid Sequence

A role for HGF/SF in neural induction and its expression in Hensen's node during gastrulation.

It was previously shown (Roberts, C., Platt, N., Streit, A., Schachner, M. and Stern, C. D. (1991) Development 112, 959-970) that grafts of Hensen's node into chick embryos enhanced and maintain expression of the L5 carbohydrate in neighbouring epiblast cells, and that antibodies against L5 inhibit neural induction by such a graft. We now show that L5 is initially widely expressed in the epiblast, but as neural induction proceeds it gradually becomes confined to and up-regulated in the early neural plate. L5 can therefore be considered as a marker for cells that are competent to respond to neural induction. We also show that Hepatocyte Growth Factor/Scatter Factor (HGF/SF) promotes the expression of L5 by extraembryonic epiblast in collagen gels after overnight culture. Explants cultured for several days in the presence of HGF/SF, as well as explants of prospective neural plate, can differentiate into cells with neuronal morphology expressing neuronal markers. To investigate whether HGF/SF is expressed in the chick embryo at appropriate stages of development, we produced specific cDNA probes and used them for in situ hybridization. We find that at the primitive streak stage, HGF/SF is expressed specifically in Hensen's node. We therefore propose that HGF/SF plays a role during the early steps of neural induction, perhaps by inducing or maintaining the competence of the epiblast to respond to neural inducing signals.

Animals

Downregulation of in vitro neurotoxicity of brain macrophages by prostaglandin E2 and a beta-adrenergic agonist.

Brain macrophages (BM), a subpopulation of microglia, have the ability to kill neurons by producing reactive oxygen intermediates. Cocultures of neurons and macrophages derived from the cerebral cortex of rat embryos were used to look for regulation of BM neurotoxicity. Isoproterenol (10(-7) M), a beta-adrenergic agonist, induced a significant inhibition of BM neurotoxicity and this effect was abolished in the presence of propranolol, a beta-adrenergic antagonist. BM neurotoxicity was also reduced in the presence of prostaglandin E2 (10(-8), 10(-6) M), a metabolite derived from arachidonic acid. These results suggest endogenous mechanisms of neuroprotection operating either during development or following lesions.

Adrenergic beta-Agonists

[Enzyme histochemical study of tha atrioventricular junction area. Correlation with slow and fast atrial pathways].

It was traditionally admitted that junctional tachycardia was based on an intranodal reentry pathway. However, lesions created at a distance from the atrioventricular node by surgery or other physical means (fulguration or radiofrequency energy ablation) demonstrated that the reentry circuit could use the slow and fast atrial pathways. This study performed in 6 human hearts less than 1 hour after death was undertaken to perform enzyme histochemical analysis of the atrial pre-nodal region. The specimens were rapidly frozen in liquid nitrogen and sliced with a cryostat. After localisation of the different regions by routine staining methods, histochemical reactions were performed using the semi-permeable membrane method for weakly bound enzyme. Ten enzymes were studied covering the principal metabolic pathways. Though routine histological stain did not show any particular structures, the enzyme histochemical reactions showed a band of myocardium following the septal insertion of the tricuspid valve, joining the orifice of the coronary sinus to the posterior part of the compact atrioventricular node. This zone of myocardium had an enzymatic make-up similar to that of the sinus node. An analogous structure was also observed above the insertion of the anterior mitral leaflet. These two regions could constitute the trajectory of the slow conduction pathways.

Adult

Influence of interleukin-1 and tumor necrosis factor alpha on the growth of microglial cells in primary cultures of mouse cerebral cortex: involvement of colony-stimulating factor 1.

The influence of monokines and CNS-derived colony-stimulating factors (CSF) on the growth of microglia has been studied in mixed glial primary cultures stemming from mouse embryos. We observed that spontaneous growth of microglial cells in the presence of astrocytes is blocked by adding anti-colony-stimulating factor 1 (CSF-1) antibodies to the cultures. Both interleukin-1 (IL-1) and tumor necrosis factor-alpha(TNF alpha) strongly increased the number of microglial cells in mixed glial cultures and this effect was prevented by anti-CSF-1 antibodies. In contrast, anti-interleukin-3 (IL-3) or anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies did not significantly affect the in vitro growth of microglia. These results provide functional significance to astrocytic productions of CSF-1 and their modulations by IL-1 or TNF alpha.

Animals

[Primary aspergillus endocarditis].

A 38-year old man was admitted for investigation of suspected endocarditis presenting with two cerebrovascular accidents and pyrexia. The initial clinical, echocardiographic and infectious investigations were normal, apart from a neutrophilic leukocytosis. The clinical course was marked by the recurrence of systemic embolism in the lower limbs, the appearance of cervical and axillary lymphadenopathy and, within a short period of time, of massive aortic valve vegetations. The diagnosis of aspergillosis was made from the culture of a peripheral embolus recovered by a Fogarty catheter and this was confirmed by the positivity of serological investigations. The patient died within two months despite antifungal therapy. Aspergillus endocarditis is characterised by its rapid progression, the volume and embolic tendency of the vegetations, the relative inefficacy of medical therapy and the potential benefits of early surgical management.

Adult

Predictive factors of effectiveness of streptokinase in deep venous thrombosis.

In a prospective study, 174 patients (118 women and 56 men, average age 44 years, range 14 to 82) with proximal extensive thrombosis received streptokinase (100,000 U/hour) for an average of 2.8 days (range 0.5 to 7) through the catheter of a temporary caval filter. Twenty-seven of 45 (60%) patients with nonocclusive clots were completely free of clots at the second phlebography versus 17 of 116 (14%) with occlusive clots (p less than 0.001). Among nonocclusive clots, proximal ones (caval, iliac and femoral) were more easily lysed than popliteal clots (88 of 116 [76%] vs 26 of 58 [45%]; p less than 0.001). In 41 of 132 (31%) patients, a daily injection of contrast medium through the filter-carrying catheter enabled the observation of a clot in the filter, which was lysed by streptokinase. Seventy patients with follow-up greater than 2 years (median 34 months) were examined clinically. Nineteen of 22 (86%) patients with venograms free of clots at discharge were free of clinical sequelae versus 16 of 48 (33%) without normal venograms (p less than 0.001). It is concluded that: (1) in the case of occlusive clots, only a few patients were normalized after streptokinase; (2) proximal nonocclusive clots were most effectively lysed; (3) when venograms were free of clots at discharge, the majority of patients did not have venous sequelae at follow-up; and (4) embolic migration seems to occur frequently with streptokinase.

Adolescent

Interleukin 1 and tumor necrosis factor-alpha stimulate the production of colony-stimulating factor 1 by murine astrocytes.

Astrocytes have the ability to secrete colony-stimulating factor 1 (CSF-1), a growth factor known to stimulate the proliferation of brain macrophages. We have studied the effect of cytokines such as interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF alpha), and interleukin 6 (IL-6) on the production of CSF-1 by cultured primary astrocytes and an astrocytic cell line derived from embryonic mouse brain. We observed that both TNF alpha and IL-1 increased CSF-1 mRNA and protein levels in the astrocytic cultures. In contrast, IL-6 was ineffective. The CSF-1 mRNA levels were strongly reduced by incubating immortalized astrocytic cells with staurosporine, a protein kinase C inhibitor, both in the absence and in the presence of cytokines. Conversely, 12-O-tetradecanoylphorbol 13-acetate, a protein kinase C activator, increased CSF-1 mRNA levels. These results suggest a mechanism whereby mononuclear phagocytes could favor their own recruitment in the CNS by producing cytokines.

Animals

Randomized trial of subcutaneous low-molecular-weight heparin CY 216 (Fraxiparine) compared with intravenous unfractionated heparin in the curative treatment of submassive pulmonary embolism. A dose-ranging study.

BACKGROUND: We compared the efficacy and safety of different dosages of a low-molecular-weight heparin, CY 216 D (Fraxiparine), in the treatment of submassive pulmonary embolism with unfractionated heparin in a prospective, randomized, dose-finding study. METHODS AND RESULTS: The primary outcome was the evolution of pulmonary vascular obstruction. We enrolled 101 patients. Four patient groups were formed: standard heparin by continuous intravenous infusion (group 1) and Fraxiparine subcutaneously 400, 600, and 900 anti-Xa Institute Choay units/kg, respectively (groups 2, 3, and 4). Inclusions were stopped prematurely in groups 3 and 4 because of the incidence of major bleedings. At day 8, the improvement of the pulmonary vascular obstruction and the major bleedings were similar in groups 1 and 2. CONCLUSIONS: The Fraxiparine dosage of 400 anti-Xa Institute Choay units/kg is as effective and safe as unfractionated heparin in the treatment of submassive pulmonary embolism.

Analysis of Variance

[Temporary caval filter allowing diagnosis and fibrinolytic therapy in patients suspect of massive pulmonary embolism].

The authors propose a therapeutic strategy enabling diagnosis, treatment and prevention in the same clinical procedure based on a series of 8 patients presenting with signs of massive pulmonary embolism (acute cardiorespiratory distress, shock, loss of consciousness, and/or cardiac arrest). A removable vena cava filter is rapidly introduced percutaneously via a brachial, femoral or jugular vein, and opened in the inferior vena cava. Using the same catheter and without a second venous puncture, pulmonary angiography and cavography are performed by digitised angiography using a small quantity of contrast medium (40 ml, 12 ml/sec). The diagnosis of massive pulmonary embolism (index of pulmonary obstruction 70 to 90%) was confirmed in 6 out of the 8 cases. In 2 patients, the contrast medium passed from the right atrium into the left atrium and one of the patients developed hemiplegia. Thrombolytic drugs (rt-PA followed by Streptokinase) were injected via the same filter catheter. The dosage of rt-PA was 20 to 50 mg as a bolus followed by 50 mg in 2 hours. Streptokinase was then infused at a dose of 100,000 U/hour for an average of 36 hours (24-48 hours), followed by intravenous heparin and oral vitamin K antagonists. Two patients required blood transfusion for haemorrhage during the relay with heparin. The temporary caval filter was removed in all cases but 3 patients required a definitive filter because of the persistence of life-threatening venous thrombosis. Seven of the 8 patients survived their pulmonary embolism. This approach is rapid, saves time, and spares the patients from more invasive procedures.

Aged