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Biomedical subjects

P Gautier

Publications and source records attributed to P Gautier.

At least 37 records · Page 2Linked to original sources
PubMed1994

SR47063, a potent channel opener, activates KATP and a time-dependent current likely due to potassium accumulation.

(i) We studied the effects of a new cromakalim analogue, SR47063, in guinea-pig ventricular cells. The experiments were carried out in whole-cell patch clamp with internal and external solutions supposedly similar to the physiological ones. (ii) SR47063 reversibly activated a time-independent current reversing near the potassium equilibrium potential, and a time-dependent current reversing at a more positive potential. Both currents were blocked by application of glibenclamide. (iii) The time-independent and the time-dependent currents were activating for the same concentration of agonist in every cell, this concentration being very different from cell to cell. (iv) The amplitude of the time-dependent current was shown to depend directly neither on agonist concentration nor on potential, but rather on the amplitude of the current flowing during the prepulse before the test pulse. (v) We conclude that SR47063 is a potent KATP channel opener acting at concentrations lower than one micromolar, and that the time-dependent current is likely due to accumulation and depletion of potassium in restricted areas of the cells.

Adenosine Triphosphate↗
PubMed1994

[Mesentric venous thrombosis. Risk factors, treatment and outcome. An analysis of 18 cases].

Eighteen patients with an acute thrombosis of the splanchnic veins were reviewed. Most of apparently idiopathic cases of splanchnic vein thrombosis are related to an increased coagulation related to a congenital or acquired defect of haemostasis. The aim of this study was to assess the effects of a new and effective treatment. Nine male and 9 female patients (range of age: 19 to 81 years) experienced a mesenteric venous thrombosis. There were 14 mesenteric vein thromboses with infarction, two transient mesenteric venous ischaemias without bowel infarction and two acute thromboses of the splanchnic veins without bowel ischaemia. A coagulopathy was detected in seven patients: oral contraception, protein C (PC) or antithrombin III (AT III) congenital deficiencies, acquired deficiency of AT III, PC and protein S (PS), polycythaemia in the post-partum period and primary myeloproliferative disorder. No coagulopathy was associated with thrombosis in eight cases: mesenteric haematoma, splenomegaly, cirrhosis, appendicectomy, cholescytectomy, chronic heart failure, treatment with beta-adrenergic receptor antagonist and digitalis, stenosis of the portal anastomosis after liver transplantation. Twelve patients required surgery: eight intestinal bowel resections with immediate anastomosis, four resections without immediate anastomosis. Only one patient underwent a second look for a repeat bowel resection. No death occurred in the early postoperative period and 17 out of 18 patients were alive after 12 years. An oral anticoagulant therapy was undertaken from two months to seven years. However, three patients suffered a recurrent thrombosis. Two of them required a long-term anticoagulation. Six patients experienced a portal hypertension and oral anticoagulants were discontinued in three of them because of bleeding oesophageal varices. Six patients were treated only by unfractionated heparin (UFH) or low molecular weight heparin (LMWH) followed by oral anticoagulants. After laparotomy, two were only treated with UFH without any bowel resection, as mesenteric venous ischaemia was too extensive. These observations suggest that the choice between an appropriate medical or surgical treatment is important and must be discussed. Since 1989, the therapeutic choice has been modified by ultrasonography and contrast enhanced computed tomographic scan which confirms diagnosis, allows to follow up and check the effects of anticoagulation and to choose the time for surgery. When the diagnosis is established and the patient's risk is low, the IU . kg(-1) . d(-1) to obtain an antifactor Xa activity between 0.3 and 0.6 antiXa IU mL(-1). When the diagnosis is uncertain and the patient's risk if high a laparotomy is required.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

[Venous thromboembolic disease in a geriatric environment. Importance of its detection and treatment].

The elderly population is particularly exposed to risk of venous thromboembolism because the risk of thrombosis increases with age but also because of the side effects of anticoagulant therapy. Clinical signs are neither sensitive nor specific and systematic screen for deep vein thrombosis in elderly patients could be justified using noninvasive techniques such as echo-Doppler or assay of D-Dimers. The aim of this study was to determine the prevalence of venous thrombosis diagnosed by echo-Doppler screening in a population of institutionalized elderly subjects. The frequency of risk factors and the cost of screening and subsequent health care were also evaluated. This study included 96 patients who underwent systematic echo-Doppler measurements. Clinical, biological and echographic data were recorded on individual file-cards for analysis. The prevalence of deep vein thrombosis diagnosis was 13.5% (13/96). All the deep vein thromboses discovered were in the popliteal area. No high risk group was found and there was found and there was no significant link with clinical signs or the level of D-Dimers. The cost of diagnosis and treatment in the particular conditions of our study were 5000 and 10,700 FRF respectively for each deep vein thrombosis diagnosed. The cost of diagnostic screening and treatment should be considered in light of the life expectancy and quality of life in this population. Thus in elderly institutionalized subjects, it would appear not to be reasonable to undertake systematic screening for venous thrombosis using echo-Doppler or D-Dimer assay.

Aged↗
PubMed1993

Free cortisol in serum assayed by temperature-controlled ultrafiltration before fluorescence polarization immunoassay.

A method is described for a temperature-controlled ultrafiltration procedure to measure free cortisol in serum. A special thermometer with a sensor was developed, measuring the temperature directly in the ultrafiltration device. The sensor is screwed on the axis of the centrifuge rotor, and the centrifuge is placed in a temperature-controlled box so that the temperature of the sample is kept at 37 degrees C +/- 0.1 degrees C. The overall CV of the free cortisol assay ranges from 2.2% to 11.4%, of which the ultrafiltration contributes only 2.2-3.6%. Increasing amounts of cortisol-binding protein, as found in women using estrogen-containing oral contraceptives, have minor but significant effects on the free cortisol concentrations in serum. Serum free cortisol concentrations in a reference population (n = 114; central 95 percentiles) were 12-43 nmol/L (4-9.5% of total cortisol); in the group of the oral-contraceptive users (n = 27), the reference interval was 11-53 nmol/L (1.5-4.5%).

Blood Preservation↗
PubMed1991

Imaging of myocardial infarction in dogs and humans using monoclonal antibodies specific for human myosin heavy chains.

The use of three different monoclonal antibodies specific for human ventricular myosin heavy chains in the visualization of the location and extent of necrosis in dogs with experimental acute myocardial infarction and in humans is described. Using a classic immunohistochemical method or ex vivo analysis of heart slices in dogs with acute myocardial infarction subjected to intravenous injection of unlabeled antimyosin antibodies or antimyosin antibodies labeled with indium-111, it was observed that all antibody fragments specifically reached the targeted necrotic zone less than 2 h after antibody injection and remained bound for up to 24 h. In a limited but significant number of cases (5 of the 12 humans and 11 of 43 dogs), it was possible to image the necrotic zone in vivo as early as 2 to 4 h after antibody injection. In other cases, individual blood clearance variations retarded or even prevented in vivo necrosis detection. Higher antimyosin fixation values were obtained in the necrotic zones in dogs with a rapid blood clearance relative to that of the other dogs. It is concluded that antimyosin antibodies always reached necrotic areas within 2 h. If blood clearance was rapid, in vivo imaging of the necrotic area was possible 2 to 6 h after necrosis, even in humans. In some cases, however, uncontrolled individual variations in the timing required for sufficient blood clearance hampered this rapid in vivo detection of myocardial necrosis.

Aged↗
PubMed1991

Detection of Borrelia burgdorferi in biological samples using the polymerase chain reaction assay.

Oligonucleotide primers were used in the polymerase chain reaction assay to amplify specific DNA regions of the Borrelia burgdorferi 49-kb linear plasmid. One set of primers identifies a 442-bp DNA fragment in the OspA gene and a second pair of amplimers, a 176-bp DNA piece located in the OspB gene. The last set of primers, OspBpc3/pc4, outperformed the other pair in discriminating pathogenic North American or European isolates from related bacterial species, detected down to 4 spirochaetes, and was suitable for the identification of B. burgdorferi in biological samples, such as synovial and cerebrospinal fluids.

Borrelia burgdorferi Group↗
PubMed1991

Effects of SR 44866, a potassium channel opener, on action potentials of rabbit, guinea pig, and human heart fibers.

The effects of various concentrations (3 x 10(-8) - 1 x 10(-5) M) of SR 44866, a K+ channel opener, on action potential (AP) characteristics were investigated in isolated rabbit sinoatrial node (SAN), rabbit Purkinje fibers, guinea pig ventricle, human atrium, and human papillary muscle. SR 44866 (up to 1 x 10(-5) M), like cromakalim and pinacidil, did not modify SAN AP and automaticity of the rabbit heart. In atrial, Purkinje and ventricular fibers of animal and human hearts, SR 44866 did not significantly change membrane resting potential, AP amplitude, or maximum rate of phase 0 (dV/dtmax). The main AP modifications induced by SR 44866 were concentration-dependent reductions in plateau amplitude and AP duration (APD): IC50 2 x 10(-7), 7 x 10(-7), 1.4 x 10(-6), 2.5 x 10(-6), and much greater than 10(-5) M for human atrium, human ventricle, guinea pig ventricle, rabbit Purkinje, and rabbit atrium, respectively. In isolated guinea pig heart, SR 44866 induced decreases in contractions (IC50 1.7 x 10(-6) M) and coronary perfusion pressure (CPP) (IC50 2.1 x 10(-8) M) with a very slight reduction (5% at 1 x 10(-6) M) in spontaneous heart rate (HR). Negative inotropic effect (guinea pig) and APD shortenings (guinea pigs and humans) of SR 44866 (1 x 10(-6) and 3.10(-6) M) were antagonized by glibenclamide (3 x 10(-7) to 3 x 10(-6) M), a specific blocker of cardiac K+ATP channels. The data support the hypothesis that SR 44866 activates ATP-sensitive K+ channels, which are present in the atria and ventricles of the human heart but not in pacemaker cells of rabbit SAN.

Action Potentials↗
PubMed1991

Fatal Streptococcus suis meningitis in man.

A case of Streptococcus suis meningitis is observed in a 39-year-old and previously healthy meat factory worker. Neurological recovery was incomplete despite adequate and sustained antimicrobial therapy. Early deafness was demonstrated by brainstem auditory evoked potentials. Death due to aspiration pneumonia, cardiac arrest and subsequent cerebral anoxia occurred late in the course of the illness.

Adult↗
PubMed1991

[Continuous Holter cardiac monitoring and chemotherapy by combination with platinum and fluoro-uracil].

Thirty-three male patients (pts) were given cisplatin and fluoro-uracil (1 g/m2/d) in IV continuous infusion over 96 h, for the primary or palliative treatment of locally advanced head and neck cancer. The mean age was 52 +/- 7 years (range: 37-65). Patients underwent continuous ECG monitoring and were monitored for 22.4 +/- 1.5 h before FU infusion, 91.9 +/- 7.3 h during FU infusion and 18.5 +/- 2 h after 5FU infusion. Patients were given one cycle of chemotherapy (32 pts), two (25 pts) or three consecutive cycles (20 pts). Seventeen pts (53%) had supraventricular arrythmia, 15 pts (47%) had ventricular arrythmia and 10 pts (31%) had ST segment deviation. The ECG abnormalities were more frequent during the first cycle of chemotherapy. No previous clinical or ECG parameter was associated to ECG changes. Platin-induced hypomagnesemia and hypokaliemia probably increase incidence of cardiac abnormalities, during and after FU infusion.

Adult↗
PubMed1990

Assay of serum cardiac myosin heavy chain fragments in patients with acute myocardial infarction: determination of infarct size and long-term follow-up.

To evaluate the correlation between myosin heavy chain release and the necrosis mass, serum levels of myosin heavy chain fragments were determined serially in 55 patients with acute myocardial infarction. Eight of these patients were successfully treated with thrombolytic agents: the others were not treated. The same myosin titration was applied to the sera of 25 dogs with an experimental myocardial infarction. Six of the dogs were successfully treated with thrombolytic agents. The time courses of the myosin concentrations are typical and monophasic for all patients with a noncomplex myocardial infarction. The values for the kinetic parameters of myosin release are comparable to those previously reported. We have now determined that cumulative myosin release significantly correlates with cumulative creatine kinase (CK), CK-MB, and lactate dehydrogenase release, as well as with thallium-201 distribution, as determined for different patient groups. Thrombolytic treatment does not seem to qualitatively upset myosin kinetics. The results obtained in dogs with or without thrombolysis conclusively indicate that myosin release is a quantitative index of the necrosis mass. From a practical point of view, a few serial determinations of serum levels of myosin heavy chains are enough to estimate the necrosed mass in patients with acute myocardial infarction. More generally, serum myosin titration could be useful in detecting any cardiac disturbance involving myocardial injury resulting in membrane leakage of cardiac cells.

Adult↗
PubMed1990

Systemic and regional haemodynamic interactions between K+ channel openers and the sympathetic nervous system in the pithed SHR.

1. The interactions between two K+ channel openers, cromakalim and SR 44866 (infused i.v. at equihypotensive doses), and the sympathetic nervous system at the systemic and regional (mesentery, kidney, hindlimb) vascular levels were investigated in the pithed spontaneously hypertensive rat (SHR) by use of the pulsed Doppler technique. 2. The two K+ channel openers did not affect postsynaptic alpha 1- but slightly reduced postsynaptic alpha 2-adrenoceptor mediated systemic pressor and regional vasoconstrictor responses. 3. Both drugs significantly decreased the systemic pressor and regional vasoconstrictor responses elicited by spinal cord stimulation. These sympathoinhibitory effects were not homogeneously distributed among the different vascular beds, the decreasing rank order being: mesentery greater than kidney greater than hindlimb. Simultaneously, the spinal cord stimulation-induced tachycardia remained unaffected. 4. After treatment with K+ channel openers, restoration of initial blood pressure and vascular tone values by infusion of prostaglandin F2 alpha (PGF2 alpha) and vasopressin respectively did not affect and abolished the sympathoinhibitory effects of cromakalim and SR 44866. 5. We conclude that in SHRs the two K+ channel openers that we investigated exert similar sympathohibitory effects which affect some vascular beds more than others. These effects are not dependent upon the arterial blood pressure level and are most likely prejunctionally located.

Animals↗
PubMed1989

Electrophysiological effects of penticainide (CM 7857) in isolated human atrial and ventricular fibers.

The intracellular electrophysiological properties of a new antiarrhythmic agent, penticainide (5 x 10(-6) to 5 x 10(-5) M) were studied in isolated driven human right atrial appendage and papillary muscle superfused with oxygenated Tyrode's solution. In atrial fibers, penticainide decreased the amplitude, maximum rate of rise (dV/dtmax), plateau amplitude, and duration (APD) of action potentials (AP). In ventricular fibers, the main AP modification induced by penticainide was a dV/dtmax diminution. All those effects were frequency and concentration dependent. Penticainide decreased resting potential at 5 x 10(-5) M only. Ventricular APD variations were relatively weak: in most of the cases, 5 x 10(-6) M decreased APD and 5 x 10(-5) M shortened long APD (greater than 300 ms) and lengthened short APD (less than 300 ms). The class I antiarrhythmic property (dV/dtmax decrease) of penticainide was rate dependent in both human fibers and was obtained at lower drug concentrations than those used in other species. The relatively rapid rate of onset and the rather slow recovery kinetics of dV/dtmax block suggest a common mechanism of action of penticainide on sodium channels in human heart and others mammals.

Action Potentials↗
PubMed1987

Electrophysiological effects of some antidepressant drugs on canine cardiac Purkinje fibres.

The electrophysiological effects of several antidepressant drugs, imipramine, metapramine, minanserin, nomifensine, and amineptine, were studied in canine cardiac Purkinje fibres at concentrations between 10(-6) mol.litre-1 and 10(-4) mol.litre-1. Metapramine (10(-5) mol.litre-1) decreased the action potential amplitude, the action potential duration, and Vmax. In addition, imipramine or metapramine induced a pronounced increase of conduction time and conduction block at 10(-4) mol.litre-1, whereas with mianserin and nomifensine a 10(-4) mol.litre-1 concentration was necessary to induce a decrease of Vmax and conduction velocity. With the exception of conduction time and action potential duration, amineptine was not able significantly to change the electrophysiological indices of canine Purkinje fibres. The decrease of Vmax observed with imipramine, metapramine, and with high concentration of mianserin and nomifensine confirms that the antiarrhythmic action of these agents might be related principally to their class I antiarrhythmic effects. The fact that amineptine, which is not antiarrhythmic, does not decrease Vmax reinforces this suggestion.

Action Potentials↗
PubMed1987

Electrophysiological studies of penticainide (CM 7857), a new antiarrhythmic agent, in mammalian myocardium.

The intracellular electrophysiologic properties of a new antiarrhythmic substance, penticainide, were studied in isolated rabbit, dog, and guinea pig myocardial preparations superfused or perfused with oxygenated Tyrode's solution. "Therapeutic" concentrations of penticainide (1.5 to 3 X 10(-5) M) had little effect on sinus node automaticity; sinoatrial conduction was slightly delayed. In atrial, Purkinje and ventricular fibers, amplitude, and maximal rate of rise of phase O (dV/dtmax) were decreased by penticainide; Purkinje-ventricle conduction velocity was depressed. Penticainide did not significantly modify action potential duration (APD) of rabbit atria and dog ventricle and reduced APD and effective refractory period (ERP) of dog Purkinje and guinea pig ventricular fibers. Penticainide reduced APD heterogeneity of Purkinje-ventricle junction with a preferential effect at the gate and decreased tension amplitude of perfused papillary muscle in dog heart. The effect of penticainide on dV/dtmax was voltage and rate dependent; the resting block was weak. Thus, penticainide is a class 1 antiarrhythmic agent with properties of class 1B agents such as APD reduction and properties of class 1C agents such as slow recovery kinetic of rate-dependent block.

Action Potentials↗
PubMed1987

Electrophysiological effects of diclofurime on rabbit and frog atrial heart muscle.

The effects of diclofurime on the electrical activity of the rabbit sinus node, rabbit atria and frog atrial fibres were studied using microelectrode and the double sucrose gap voltage-clamp techniques respectively. In rabbit sinus node, diclofurime (10(-7) M to 10(-6) M) decreased the action potential (AP) amplitude and maximum rate of depolarization (Vmax), increased the AP duration and slowed the sinus rate. In rabbit atria, the drug reduced the amplitude of the depolarizing phase and Vmax, lengthened the AP duration and decreased the resting membrane potential. In frog atrial fibres, the drug (10(-5) M) depolarized the resting membrane potential, decreased Vmax as well as the plateau amplitude. It inhibited the sodium current (INa) with a dissociation constant of 3.7 X 10(-6) M and a one to one relationship between the drug molecule and the Na channel. Diclofurime did not alter the apparent reversal potential for the fast Na current (ENa) but it inhibited the sodium conductance (GNa) in a frequency-dependent manner. Diclofurime also blocked the slow inward current (Islow) without alteration of Eslow. The block of Islow occurred with a dissociation constant of 2 X 10(-5) M and unity stoichiometry. The data suggest that diclofurime might be effective in the control of cardiac arrythmias since it exhibited both local anaesthetic-like and calcium antagonistic properties.

Action Potentials↗
PubMed1987

[Ruptured lutein cyst associated with undiagnosed contralateral tubal pregnancy].

We are dealing with the case of a patient suspected of ectopic pregnancy. Laparoscopy showed a ruptured corpus luteum on the right side with haemoperitoneum. Four days after her discharge, she came back with a ruptured ectopic pregnancy in the outer third of the left tube. We emphasize the difficulties of an early diagnosis of ectopic pregnancy and its etiology.

Adult↗