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Biomedical subjects

P Mathieu

Publications and source records attributed to P Mathieu.

At least 73 records · Page 4Linked to original sources

L-arginine prevents cyclosporin A-induced pulmonary vascular dysfunction.

BACKGROUND: Cyclosporin A is known to alter endothelium-dependent responses to different agonists. Few data are available concerning the effect of cyclosporin A on the pulmonary vascular bed. METHODS: The endothelium-dependent responses to acetylcholine (20 micrograms), bradykinin (5 micrograms), and substance P (5 micrograms) were investigated in a dog model of left lung autoperfusion at constant flow. RESULTS: The vasodilator response to bradykinin and substance P was significantly decreased with cyclosporin A (20 mg) administration. The average decreases in pulmonary arterial pressure with bradykinin were 5.4 +/- 1.5 mm Hg and 2.4 +/- 0.4 mm Hg before and after cyclosporin A administration, respectively (p = 0.04). The average decreases in pulmonary arterial pressure with substance P were 4.4 +/- 1.0 mm Hg and 1.8 +/- 0.5 mm Hg before and after cyclosporin A administration, respectively (p = 0.04). The responses to acetylcholine and the endothelium-independent relaxing agent nitroglycerin were not significantly affected by cyclosporin A. The effects of cyclosporin A on endothelium-dependent responses to bradykinin and substance P were overcome by the administration of L-arginine (200 mg/kg intravenously). The decreased response to bradykinin and substance P after cyclosporin A administration was not significantly affected by indomethacin, a cyclooxygenase inhibitor. The pulmonary angiotensin-converting enzyme activity was also measured using [3H]benzoyl-phenylalanyl-glycyl-proline, an inactive angiotensin-converting enzyme substrate. There was an average [3H]benzoyl-phenylalanyl-glycyl-proline hydrolysis of 54% +/- 2% and 55% +/- 2% before and after cyclosporin A administration, respectively (not significant). CONCLUSIONS: The present study suggests that cyclosporin A selectively decreases endothelium-dependent responses to bradykinin and substance P without affecting the cyclic guanosine monophosphate-dependent pathway in the canine pulmonary vascular bed. The decreased endothelium-dependent responses to bradykinin and substance P are not related to increased angiotensin-converting enzyme activity. The toxic effect of cyclosporin A on endothelium-dependent responses is reversible by the administration of L-arginine, a source of substrate for nitric oxide.

Acetylcholine↗

The effects of position on the radiographic joint space in osteoarthritis of the hip.

The aim of the study was to assess whether radiographic hip joint space thickness was changed by weight-bearing (WB) compared with non weight-bearing (NWB) position, and to evaluate whether radiographs centered on the hip were more sensitive than pelvic X-rays to detect such a change. Anteroposterior radiographs of the pelvis were made in 30 patients with hip osteoarthritis OA (46 OA and 11 normal hips). Osteoarthritic, as well as contralateral normal hips were analyzed. Radiographs centered on OA hip were performed in 28 other patients. X-rays were made in WB and NWB positions using a standardized radiological procedure. Measurements of mean joint space width (MeanJSW) maximum joint space narrowing (MaxJSN) and joint space surface area (JSA), were made using a computerized image analysis system. The joint space width was unaffected by WB in normal joints but decreased with WB in OA joints. The decrease was significant only when considering MaxJSN in patients with a joint space thickness smaller than 2.5mm. The difference between WB and NWB was larger in radiographs centered on the hip than on pelvic X-rays. MeanJSW and JSA were found to be less sensitive than MaxJSN. The decrease of joint space width was inversely correlated with joint space size in WB. These results suggest that WB radiographs of the hip should be used in preference to NWB in studies of hip OA.

Aged↗

[Cyclosporine A prevents ischemia-reperfusion induced myocardial dysfunction in the isolated heart of the rat].

Cyclosporin A (CyA) has been shown to prevent mitochondrial injury following ischemia-reperfusion injury. Therefore, the present study was designed to investigate the effect of CyA on ischemia-reperfusion injury in the isolated rat heart preparation. Hearts from Sprague-Dawley rats were perfused in the Langerdorffmode at constant pressure (80 cm H2O) and paced (270 beats/min). After equilibration, hearts were treated with CyA (10(-5) mol/l) (n = 8) or its vehicle, cremophor (Cr) (n = 8) for 10 minutes before exposure to 30 minutes of global ischemia and 60 minutes of reperfusion. Hemodynamic variable vascular reactivity, and oxygen consumption (MVO2) were tested at baseline and at selected points during reperfusion Hemodynamic variables were significantly improved in the CyA group. The maximal mean percentage of preservation for left ventricular developed pressure (PDVG) was -14.9 +/- 10.7% and +31.5 +/- 23.6% respectively for Cr and CyA group (p<0.05) The maximal mean percentage of preservation for dp/dt was -11.7 +/- 11.4% and +28.3 +/- 29.9% respectively for Cr and CyA group (p < 0.05): the compliance, -dP/dt was also preserved, maximal mean preservation was -25.9 +/- 9.2% and +53.1 + 30.1% respectively in Cr and CyA group (p < 0.01). Oxygen debt was decreased at 30 minutes of reperfusion in the CyA-treated hearts: 0.06 x 10(-2) +/- 0.23 x 10(-2) cc/min/g compared to Cr-treated hearts: 0.61 x 10(-2) +/- 0.37 x 10(-2) cc/min/g (p = 0.05). The coronary endothelial dependent and independent responses were similarly decreased in both groups during reperfusion. Thus, in the isolated rat heart preparation, CyA preserves myocardial function (hemodynamic variables) and oxygen consumption without affecting the coronary vascular function during ischemia-reperfusion injury.

Animals↗

-Knee prosthesis-.

The initial radiological assessment of knee osteoarthritis includes the evaluation of the osteochondral destruction, collateral ligament laxity and the determination of the position of the patella in both the axial and the sagittal planes and the femorotibial angulation in the coronal plane. The different types of knee prostheses are described. Post-operative radiological features of knee arthroplasties are discussed including normal findings and criteria of prosthesis instability and loosening.

Arthroplasty, Replacement, Knee↗

[The medial collateral ligament of the knee].

Injuries of the medial collateral ligament (MCL) of the knee are easily diagnosed on clinical grounds. These lesions are generally treated conservatively. Radiological examinations are generally unhelpful. However, injuries of the MCL may be associated with those of many other ligaments of the knee in the case of complex strain of the knee so that the clinical diagnosis may be challenging; in some cases, surgical repair of associated lesions is indicated. In these cases of multiple ligamentous injuries, a radiological study of ligamentous abnormalities may be of interest. The anatomical background and the different radiological findings including those of X-rays, US, arthrography and MRI, obtained in patients with injuries of the MCL, are described; radiological differentiation of ruptures of the MCL with or without knee instability is emphasized.

Arthrography↗

A 5-year (1990-1994) neuroblastoma screening feasibility study in France. Methodology and preliminary observations.

INTRODUCTION: Following the pioneering Japanese experience, several European and North American groups implemented pilot studies on screening infants for neuroblastoma, considering the possibility of demonstrating a decrease in mortality rate. In France, a 5-year (1990-1994) feasibility study on neuroblastoma screening at the age of 4 months was initiated in the Rhône district (1.5 M inhabitants, 26,000 births per year). METHODS: Vanillylmandelic (VMA) and homovanillic (HVA) acids were measured by HPLC, and creatinine (Cr) by the Jaffé's kinetic method on Technicon RA-XT. VMA and HVA were expressed as microgram/mg of Cr. The method was assessed with both a daily intra-laboratory control and a sample of urine obtained from a national quality control organism. RESULTS AND DISCUSSION: The overall participation rate for the 5-year period was 82.2%. Out of 105,293 infants tested from 128,126 births, 12 NB cases were discovered with screening (screened cases) and 1 case was discovered with a late performed test (at 13 months of age). Six neuroblastomas were found clinically before the age of 4 m. Two cases were missed because the parents did not perform the test. Three children with normal tests at screening were false-negative cases: two of them were found secreting at diagnosis, while one remained non-secretory at diagnosis and later on. Otherwise, thirty-five false-positive tests were found. Biochemical observations are discussed. It is too early to reach clinical conclusions from this screening program on neuroblastomas as it is presently being followed up.

Chromatography, High Pressure Liquid↗

Increased serum levels of neuron-specific enolase in epileptic patients and after electroconvulsive therapy--a preliminary report.

Serum neuron-specific enolase (NSE) levels were studied by an enzymo-immunoassay method in 2 groups of patients: a group of epileptic patients, and a group of patients with refractory major depression after electroconvulsive therapy (ECT). In patients without organic neurological disease (n = 274) the mean serum NSE level (+/- S.D.) was 8.4 +/- 3.4 micrograms/l. No correlation with sex or age was observed. No significant difference was observed between epileptic patients without seizure or major electroencephalogram (EEG) abnormality, and a reference group. Significant increases were observed in 32 samples collected from patients with interictal EEG without spikes and waves before the 7th day after a seizure, in whom mean NSE was 21.5 +/- 9.4 micrograms/l, and in 26 samples from 4 patients without seizures but with spikes and waves in the interictal EEG, whose mean NSE was 20.6 +/- 11.5 micrograms/l. The increases of serum NSE levels in epileptic patients seem therefore to be linked to seizures and/or to EEG abnormalities. The consequences of these observations for the survey of epileptic patients, and for the diagnosis of cerebral tumors (mainly neuroblastoma) or for monitoring treatment after surgical resection, are discussed. In only 1 patient out of 6, an increase in serum NSE levels was observed with a peak about 12 h after ECT. No significant correlation with the ECT features (length of seizures, one- or two-sided electrodes) was observed.

Adult↗

Comparison of the diagnostic and prognostic value of biological markers in neuroblastoma. Proposal for a common methodology of analysis. SENSE group.

BACKGROUND: The prognosis of pediatric neuroblastoma depends both on clinical presentation and on certain cellular and molecular characteristics. Screening programs have been initiated in infants of less than one year of age, based on the hypothesis that neuroblastoma progresses from early to late clinical stages through a classical multistep process linked to an accumulation of molecular abnormalities. However, recent analyses suggest that most cases discovered by screening are low stage tumors considered as dysembryogenetic residues devoid from major abnormalities and that high-grade tumors with molecular abnormalities are unrelated diseases. AIM OF THE REVIEW: To confirm one or the other hypothesis, and eventually identify biological factors possibly responsible for the initiation and progression of the disease, it is of utmost importance that all investigators agree on biological criteria for analysis when neuroblastoma tissue is available in screened and unscreened populations. This paper reviews the biological tools available for prognosis in neuroblastoma, the priority for analysis of biological markers according to both methodological reliability and feasibility, and the conditions of tissue storage for further analysis of these biological markers. CONCLUSION: The standardized biological evaluation of neuroblastoma will allow to collect sufficient data for multivariate analysis; such analysis is now fundamental if one wants to clearly define the respective impacts of biological abnormalities on neuroblastoma progression.

Biomarkers, Tumor↗

[Antiaggregant effect and tolerance of calcium carbasalate administrated immediately after aorto-coronary bypass. Results of a double-blind versus placebo study].

The patency of aorto-coronary bypasses is greatly influenced by platelet aggregability, and there is an associated risk of thrombosis which may occur very early during surgery. It is in this context that aspirin has been the subject of successful clinical studies. When administering aspirin, it is preferable to choose formulations that are well tolerated by the gastro-intestinal tract. This was the reason for carrying out the present randomised single-centre double-blind parallel-group study aimed at confirming the platelet anti-aggregant effect and tolerability of calcium carbasalate administered during the immediate postoperative period. The dose prescribed was equivalent to aspirin 325 mg daily, and was given as a single dose 6 hours after the end of the operation and repeated for 7 days, versus placebo, in 56 patients undergoing aorto-coronary bypass grafts. A clinical assessment, ECG, platelet count and measurements of CPK and CPK-MB were carried out daily for the 7 days of the study. Tests of platelet aggregation (to arachidonic acid, ADP and collagen), assays of serum thromboxane B2, MDA and PDF, and urinary assays for beta-thromboglobulin and 6-keto-PGF-1 were carried out before treatment, then 1 and 7 days after the start of treatment. Fifty males (89%) and 6 females, mean age 58.3 years, received treatment with either calcium carbasalate (group C, n = 28) or placebo (group P, n = 28). The atheromatous lesions present in most cases represented triple-vessel disease (37 cases), and most operations were triple bypasses (23 cases) or double bypasses (20 cases). A significant reduction in platelet aggregation to arachidonic acid and collagen on D1 (p = 0.05) and D7 (p < 0.001), and to ADP on D7 (p < 0.01) was observed in group C as compared with group P. Group C also showed significant reductions as compared with group P in respect of serum thromboxane B2 levels on D1 (p < 0.01) and D7 (p < 0.001) and MDA levels on D1 and D7 (p < 0.001). No significant difference was demonstrated between the two groups in respect of urinary 6-keto-PFG-1 excretion. The number of patients showing a rise in CPK was lower in group C but this difference did not reach statistical significance. ST segments change were comparable in the two groups, and no patient complained of anginal pain during the study. These results show that calcium carbasalate administered at a dose equivalent to 325 mg aspirin daily caused very early inhibition of platelet aggregation, specifically inhibiting platelet production of thromboxane B2 without altering prostacyclin levels. In addition, calcium carbasalate was found to be well tolerated. This study confirms the value of early administration of aspirin at a dose of 325 mg daily during the hours immediately following aorto-coronary bypass graft surgery.

6-Ketoprostaglandin F1 alpha↗

[Effect of cyclosporin A dosage on the vascular tone of the thoracic aorta of rats].

Cyclosporine A (CyA) is known to affect the local release of endothelial-derived relaxing factor (EDRF). However, evidence that CyA could specifically alter endothelial signal transduction is not well understood. Experiments were designed to assess dose-dependent effect of CyA on vascular reactivity-specificity of the rat thoracic aorta. Three groups of rats (n = 10) were treated for 4 weeks with oral CyA 15 mg/kg/day (Gr 1), CyA 30 mg/kg/day (Gr 2), and olive oil (Gr 3), the CyA vehicle. At the end of the period, animals were euthanized and the thoracic aorta harvested for isometric assessment of endothelial and smooth muscle function in organ chambers. Maximal endothelial-dependent relaxation (Rmax) to acetylcholine dose-response was similarly affected in rats treated with CyA [Rmax (%): Gr 1: 33 +/- 8, Gr 2: 28 +/- 2, Gr 3:51 +/- 7, *p < 0.05]. At the opposite, response to adenosine diphosphate [Rmax (%): Gr 1: 11 +/- 2, Gr 2:24 +/- 3*, Gr 3:7 +/- 2, *p < 0.01] and histamine [dose-response CE50 (log M): Gr 1: +/- 12 +/- 0.05, Gr 2: +/- 5.45 +/- 0.05*, Gr 3: -4.85 +/- 0.08, *p < 0.05] were significantly enhanced in animals exposed to 30 mg/kg/day. Endothelium-independent relaxation to sodium nitroprusside (SNP) was comparable in all groups and dose-response to depolarizing (KCl) and non-depolarizing (norepinephrine) contractile agents were not affected either. These experiments suggest that CyA does not affect second messenger (cyclic-GMP) activation by an EDRF analogue (SNP) whereas signal transduction coupled to muscarinic, purinergic, and histaminergic receptors are either inhibited or enhanced by CyA in dose-dependent manner in the rat aortic model.

Animals↗

[Effect of cyclosporin A on the reactivity of the pulmonary vascular network in dogs].

UNLABELLED: Aside to its immunosuppressive effects, cyclosporine A (CyA) is known as a vasoconstrictor agent. The vasoconstriction appears to be related to an endothelial release of thromboxane A2 (TxA2) and endothelium as well as a decrease endothelial production of nitric oxide. However, no data is available on the effects of CyA on pulmonary artery (PA) network. We designed experiments to study the CyA effects on canine pulmonary artery vasoregulation. Resistance vessels were studied in vivo using a lung (n = 6) steady rate delivery autoperfusion model. The CyA was infused in the left pulmonary artery at incremental doses of 5, 10, and 20 mg; CyA dosage, sampled in the left atrium, were respectively 515 +/- 67, 580 +/- 97, and 1024 +/- 84 nmol/L. No significant increase in tension were registered regardless of the dose infused. Conductance vessels were studied in vitro using third division PA segments (n = 6) suspended for isometric force measurement in organ chambers. PA segments were precontracted (phenylephrine 10(-6) M) and subsequently exposed to incremental dose of CyA and cremophor (CR), the CyA vehicle. CyA specifically induced a dose-dependent contraction. The maximal contraction observed were 159 g +/- 13% with CyA exposure and 106 +/- 3% with the CR (p < 0.05). This contraction was abolished by indomethacin (cyclooxygenase inhibitor), pinane thromboxane A2 (TxA2 antagonist), dexamethasone (phospholipase A2 inhibitor), neomycin (phospholipase C inhibitor), and endothelial mechanical denudation. CONCLUSIONS: In the canine model, in vivo infusion of CyA does not affect pulmonary resistance arteries. However, in vitro, on pulmonary conductance arteries, CyA induces an endothelium-dependent vasoconstriction. This constriction appears to be related to a TxA2 release mediated by a phospholipase A2 phospholipase C pathway.

Animals↗