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Biomedical subjects

P Colson

Publications and source records attributed to P Colson.

At least 37 records · Page 2Linked to original sources

[Vascular effects of adenosine-triphosphate].

This study assessed the effects of adenosine triphosphate (ATP) on systemic vascular resistances during the hypothermic cardiopulmonary bypass phase of cardiac surgery. Twenty patients scheduled for cardiac surgery were randomly divided into an ATP group (n = 10), and a placebo group (n = 10). Anaesthesia was similar for all the patients (diazepam, fentanyl and pancuronium). During the heart arrest phase, and as soon as the arterial pressure, the level in the venous return reservoir, and the pump flow rate had all been in steady state for 5 min, ATP or placebo was injected into the venous line of the oxygenator. Injection speed was doubled every three minutes, twice. The following ATP doses were administered: 0.012, 0.025 and 0.05 mg.kg-1.min-1. The level in the venous return reservoir was kept constant. Mean arterial pressure (MAP) and pump flow rate (DP) were assessed every half minute. Systemic vascular resistances were calculated with the relationship MAP/DP. Changes in vascular capacitance were directly proportional to changes in DP as the heart had been excluded, and all the blood returned to the pump, the blood volume being kept constant. MAP and DP remained unchanged in the placebo group. In the opposite ATP induced a dose-related systemic vasodilation: MAP decreased from 82.8 +/- 12.5 mmHg (control) to 66.0 +/- 14.8 mmHg, 59.8 +/- 10.6 mmHg, and 49.0 +/- 4.7 mmHg with 0.012, 0.025 and 0.05 mg.kg-1.min-1 ATP respectively. The MAP returned to preinfusion control levels when the ATP infusion was discontinued (90.0 +/- 17.8 mmHg). The DP, and therefore venous return, did not change, neither during ATP infusion, nor after its discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

[Simplified strategy for anesthesia of pheochromocytoma].

The only curative treatment of phaeochromocytoma consists in surgical removal. This carries a high risk due to the acute release of catecholamines. General anaesthesia cannot by itself prevent haemodynamic disturbances during surgical manipulation of the tumour. Careful preparation, based on intravascular volume repletion as well as alpha-, and, if required, beta-adrenergic blockade, has been shown to reduce morbidity and mortality. However, this protocol is often cumbersome, and does not prevent totally the haemodynamic instability as a decrease in blood pressure at the start of treatment, or after removal of the tumour. Since voltage-dependent calcium channels are involved in both secretion and action of catecholamines, calcium-channel antagonists might be an interesting therapeutic alternative. In fact, short-term treatment by dihydropyridines may attenuate blood pressure variability during the preoperative period. During surgery, a dose-dependent reduction in systemic vascular resistances has been shown with intravenous nicardipine. However, dihydropyridines do not control cardiac adrenergic stimulation, which causes tachycardia or persistently increased blood pressure in spite of low or normal systemic vascular resistances. Such an acute cardiac hyperactivity, which can only be assessed by continuous haemodynamic monitoring, is electively sensitive to a beta-adrenergic blocker rather than a calcium channel antagonist with high cardiac affinity (diltiazem, verapamil). Esmolol is available for intravenous administration. It is an ultra-short acting agent, ensuring a selective dose-related cardiac beta 1-blockade. Combining esmolol with nicardipine gives control over almost all episodes of haemodynamic worsening during phaeochromocytoma resection. Preoperative medical treatment no longer aims to suppress adrenergic stimulation completely, but to prevent acute haemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms

Condensation and precipitation of chromatin by multivalent cations.

The condensation and the precipitation of rat liver chromatin upon addition of spermine4+, spermidine3+, hexamminecobalt(III)3+ and Mg2+ cations have been studied using solubility, fluorescence, circular dichroism, melting curves, electric dichroism and spermidine binding measurements, made on both soluble and precipitated complexes. The soluble complexes obtained with tetra- and trivalent cations were depleted from all histones and enriched in other proteins, particularly high mobility group proteins 1 and 2, which brings about an important enhancement of tryptophan fluorescence without modification of its two lifetimes 5.1 and 1.2 ns. In the precipitates the non-histone proteins are eliminated. Under precipitation by Mg2+ ions, the distribution of proteins remains practically unchanged. The electric dichroism and the melting curves indicate that the soluble complexes between polyamines and chromatin undergo important condensation and, at high ratios of cation over phosphate, are constituted by heterogeneous assemblies of non-histone proteins and DNA. On the contrary, the insoluble complexes seem to retain the main features of original chromatin. Precipitation by Mg2+ ions reveal much less drastic changes than those produced by polyamines. Precipitation by spermidine occurs when one cation is bound per eight nucleotides, which in addition to the histone positive charges brings about a complete neutralization of chromatin phosphates.

Animals

Molecular recognition between oligopeptides and nucleic acids. DNA sequence specificity and binding properties of an acridine-linked netropsin hybrid ligand.

The binding to DNA of a mixed function ligand (NETGA) is described, in which a potential intercalating group, an acridine moiety, is incorporated at the carboxyl terminus of the minor groove binding oligopeptide netropsin skeleton. Scatchard analysis of absorption data provided evidence of two modes of binding to DNA with K1 = 9.1 x 10(5) M-1 at low r values (0.003-0.1), and a binding site size n = 10, indicative of binding of both moeities. At high binding ratios (greater than 0.1), K2 = 0.9 x 10(5) M-1 and n = 5 corresponding to external binding. Complementary strand MPE footprinting on a pBR322 restriction fragment showed NETGA binds to 5'-AAAT like netropsin. It causes enhanced cleavage by MPE, particularly at G-C rich sequences and remote from the preferred binding sites. Viscometry measurements provided evidence for biphasic modes of the two binding portions of NETGA. Fluorescence polarization and linear dichroism measurements were in accord with distinct modes of interaction of the acridine (intercalation) and oligopeptide (minor groove binding) portions of NETGA. LD measurements on NETGA indicate that the oligopeptide moiety (netropsin-like) has an orientation typical of minor groove binders, whereas the degree of intercalation of the acridine group is decreased by association of the oligopeptide moiety.

Aminoacridines

Organic osmotic effectors and chromatin structure.

Organic amino compounds (taurine, glycine) and polyols (mannitol, sorbitol) are used as osmotic effectors by most animal cells, particularly by some marine invertebrates, but also to a limit extent by mammalian cells. Using physico-chemical techniques (circular dichroism, thermal denaturation, solubility, electrophoresis and electric linear dichroism), we demonstrated that some of these effectors prevent chromatin aggregation, without histone release. The influence of glycine on chromatin aggregation, dissociation and reconstitution was thoroughly investigated. Glycine at 2 M concentration does not in itself induce chromatin dissociation; it does hinder salt-induced histone dissociation from chromatin (especially at 1.2 M NaCl) but does not impede chromatin reconstitution. Several hypothesis may be put forward to explain the action of these effectors: (i) a modulation of histone conformation; (ii) a modification of fractional DNA charge, either directly by the zwitterions (glycine, taurine) or indirectly by alteration of cations counterions hydration. The physiological relevance of our experiments is also discussed.

Animals

Effect of angiotensin converting enzyme inhibition on blood pressure and renal function during open heart surgery.

Activation of the renin-angiotensin system during open heart surgery may have consequences both beneficial in sustaining blood pressure and deleterious in compromising renal hemodynamics. The influence of short-term pretreatment with captopril on blood pressure and renal function was assessed double-blind versus placebo in 18 patients without pre-existing cardiac or renal failure, and undergoing coronary artery bypass. No difference in blood pressure and fluid requirement during the surgical period was observed between groups receiving captopril or placebo. Effective renal plasma flow and glomerular filtration rate decreased in the placebo group whereas they remained unaltered in the captopril group; during cardiopulmonary bypass, urinary excretion of sodium was greater in patients receiving captopril than those receiving placebo. These results suggest that captopril pretreatment does not compromise the control of blood pressure and renal function during open heart surgery; additional studies on the protective value of angiotensin-converting enzyme inhibitors are warranted in patients at higher risk for developing renal failure.

Angiotensin-Converting Enzyme Inhibitors

[Pre- and postoperative antihypertensive treatment with calcium antagonist in pheochromocytoma].

Medical preparation for pheochromocytoma surgery requires adrenergic blockade and restoration of euvolemia. Usually, this preoperative preparation consisted essentially of sequential and progressive adrenergic antagonism, alpha then beta blockade. This therapy is not easy to introduce and exposes to blood pressure collapses after tumor removal. By contrast, calcium channel blocking drugs like dihydropyridines offer efficacy and safety. Moreover, new intravenous (IV) agents (nicardipine, diltiazem) provide useful therapeutic tools to control, rapidly and with a dose-dependent effect, any undesired hemodynamic event during surgery. As a demonstration of this new therapeutic strategy for management of pheochromocytoma resection, we report here the cases of two patients who were exclusively treated with dihydropyridines. A 61 year-old woman and a 41 year-old man were scheduled for pheochromocytoma resection (left and right adrenal tumors, respectively). Both patients received dihydropyridines for preoperative preparation (nicardipine and nifedipine, respectively, 60 mg/day). This treatment allowed a good control of arterial blood pressure (BP) (from 210/110 to 170/90 and 180/100 to 140/80 mmHg, respectively) and was maintained up to the morning of the operative day. After patient installation on the operating-table, IV nicardipine infusion was started (2 mg/hour). Anesthesia consisted of high doses of fentanyl, flunitrazepam and vecuronium. Hemodynamic measurements (radial artery and Swan ganz catheters) allowed adjustment of nicardipine infusion rate to maintain peripheral arterial resistances under 1,000 dynes.s.cm-5, and adequate volume loading. A hypertensive crisis (270/130 mmHg) occurred at the time of the intubation in the first case but responded to higher infusion rate of nicardipine (5 mg/10 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms

Polyamine addition to preparation media induces chromatin condensation, irreversibly at low ionic strength.

Polyamines (spermine, spermidine) are commonly used as stabilizing cations in the chromatin preparation media. Their residual binding to chromatin is not easily reversed at low ionic strength, even after extensive dialysis, as evidenced by the use of labelled spermidine. Electric dichroism measurements show that their presence interferes with the physico-chemical characterization of chromatin by maintaining a condensed structure. These results give a definite answer to the controversy about the sign of optical anisotropy of chromatin determined by electric and flow dichroism techniques.

Animals

Electric and flow linear dichroism of unfolded and condensed chromatin: a comparative study at low and intermediate ionic strength.

Identical samples containing polynucleosomal chains of chicken erythrocyte (CE) and Ehrlich ascites tumour (EA) chromatin were studied under various ionic conditions with regard to electric linear dichroism (ELD) and flow linear dichroism (FLD). Both orientation techniques consistently confirmed that, in the limit of very low ionic strength and in the absence of multivalent cations, the reduced linear dichroism of chromatin is negative in the DNA-base absorption band, as expected for an extended zig-zag polynucleosomal conformation. With increasing electrolyte content, both ELD and FLD decreased drastically in amplitude, but in contrast to the ELD which remains negative in an intermediate range of low ionic strength (0.1-0.5 mM Mg2+) the FLD changes sign and becomes positive. The ELD and FLD amplitudes decrease with higher Mg2+ concentrations and FLD even vanishes in the region of 0.2-0.4 mM; both signals are positive above 0.4-0.5 mM Mg2+. The origin of the dissimilarities between ELD and FLD observations is still not fully understood. Several possibilities are considered: ELD signals are more influenced than FLD by the presence of short chromatin chains, nucleosomes and small pieces of naked DNA, while FLD is more susceptible to the presence of large, easily orientable, scattering aggregates. Different preferred orientation directions of the chromatin fibre with respect to electric and hydrodynamic fields may also be involved. Finally, FLD and ELD probably "see" different features of the chromatin structure.

Animals

Is epidural anaesthesia using bupivacaine safe in patients with atrio-ventricular conduction defects?

Bupivacaine is known to interact with the conductive system of the heart, also when used in epidural anaesthesia. Ten patients, undergoing bupivacaine epidural anaesthesia for lower limb or pelvic surgery, who presented a history of cardiac conduction disturbances, were studied. The ECG was continuously monitored and a right ventricular bipolar electrode was used to monitor the following parameters: heart rate, QRS duration, QT, Atria-His and His-Ventricle intervals. No significant change was noticed, even in patients with a high grade conduction defect. The mean plasma level of bupivacaine was 0.33 +/- 0.23 micrograms/ml. Based on this experience, it seems that lumbar epidural anaesthesia with bupivacaine can be safely used in patients with asymptomatic AV conduction abnormalities.

Anesthesia, Epidural

Synthesis, biological activity and DNA interaction of anilinoacridine and bithiazole peptide derivatives related to the anti-tumor drugs m-AMSA and bleomycin.

The synthesis of two depsipeptides including a peptide metal-chelating moiety (Gly-His-Lys) and a moiety with DNA affinity, namely either glycyl-anilino-9-aminoacridine 1 or 2'-(2-aminoethyl)-4-methoxycarbonyl-2",4'-bithiazole 2, has been carried out. The goal was to introduce separately on the same molecule the two factors contributing to the biological activity of many anti-tumor drugs. The interaction of both drugs with DNA has been studied and the acridine ring of 1 was found to intercalate in the double helix. The production of free radicals has been evidenced by spin-trapping for 1 although both compounds were revealed to be good copper-chelating agents. In vitro cytostatic activity and inhibition of [3H]-thymidine incorporation were obtained for 1 while 2 exhibited no activity in both tests. In view of these results, it can be pointed out that the anti-tumor properties of such drugs rely (1) on their ability to reach and to bind DNA and (2) on redox mechanisms involving interactions between the drugs, metals and molecular oxygen. The latter phenomenon leads to the formation of active radical species, able to degrade the DNA.

Aminoacridines

[Pulse oximetry and thoracopulmonary surgery].

Arterial blood gases are invasive and they provide intermittent information only. On the other hand, pulse oximetry is non invasive, providing continuous monitoring of SaO2 (SpO2). A study was therefore carried out in twelve patients undergoing lung and intrathoracic surgery to determine whether pulse oximetry was a reliable method of monitoring. The SpO2 values obtained using a Physiocontrol Oximeter (Lifestat 1600) were compared with those given by blood gas measurements (SaO2). When ventilation was switched to one-lung ventilation, PaO2 fell in all cases, whatever the method of monitoring, with PaCO2 remaining constant. 46 paired values of SaO2 were compared using linear regression analysis. Correlation between the two methods was good (r = 0.95; p less than 0.001). Pulse oximetry would therefore seem to provide a reliable method of continuous noninvasive and accurate monitoring of oxygenation during lung surgery.

Adult

Comparative study of the condensation of chicken erythrocyte and calf thymus chromatins by di- and multivalent cations.

The condensation of chicken erythrocyte (CE) and calf thymus (CT) chromatins upon addition of di- and multivalent cations has been studied using turbidity, precipitation and electric dichroism measurements. For all the cations investigated (Mg2+, Tb3+, Co(NH3)6(3+), spermidine Spd2+ and spermine Sp4+) condensation of CE chromatin occurred before the onset of aggregation, while aggregation of CT chromatin started before condensation with all cations except Mg2+ and Tb3+. Precipitation of CE chromatin required lower di- and multivalent cations concentrations than CT chromatin. The electric dichroism data for both chromatins, at low ionic strength in the absence of di- or multivalent cations, indicated that the nucleoprotein molecules were not totally decondensed but that a "precondensed" state was already present. A positive electric dichroism was observed for the most condensed chromatin fibers, in agreement with the "cross-linker" models. Tb3+ led to less compact condensed particles as judged from the electric dichroism observations, but electron microscopy revealed that "30 nm fibers" were formed. Very little aggregation was produced by Tb3+. On the contrary, spermine produced very large networks of condensed molecules, but large spheroidal particles were also observed. The condensation of CE chromatin happened without changes of solution conductivity upon cation salt addition, regardless of the condensing cation, indicating a cooperative uptake of the ions during this process.

Animals