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Biomedical subjects

P Colson

Publications and source records attributed to P Colson.

At least 127 records · Page 7Linked to original sources
PubMed1992

Fibrin sealant for early repair of acquired ventricular septal defect.

The trend toward early operation for acquired ventricular septal defects exposes the patient to major perioperative bleeding and residual shunt because of the fragility of the recently necrosed myocardium. To reduce these complications we have used a fibrin sealant to reinforce the cardiac tissues in addition to the usual closure of the defect with a Dacron patch through a left ventricular septum around the defect, area. During cardiac arrest fibrin sealant is applied on the ventricular septum around the defect, between the septum and the patch, and on the edges of the ventriculotomy. This technique was used in three patients (mean age 68.2 years) operated on for an acquired ventricular septal defect within 4 days of the infarction and within 24 hours of the occurrence of the defect. Low postoperative bleeding, absence of recurrent shunt, and good ventricular function indicated satisfactory surgical result in all three patients. We suggest that the use of fibrin sealant during operations for acquired ventricular septal defects, by reinforcing the necrotic and fragile tissues, may reduce perioperative bleeding and assure a more solid implantation of the patch.

Adult↗
PubMed1992

Relationship between DNA-binding and biological activity of anilinoacridine derivatives containing the nucleic acid-binding unit SPKK.

The synthesis of two peptidic derivatives, including an anilinoacridine chromophore (related to the antileukemic drug amsacrine) and either the tetrapeptide SPKK (a nucleic acid-binding unit) (1) or the octapeptide SPKKSPKK (2), has been carried out. The interaction of both drugs with DNA has been studied. Binding data are consistent with a model in which the acridine nucleus occupies an intercalation site and the tetrapeptidic or octapeptidic portion is located in the DNA minor groove. Compound 1 fully intercalates into DNA. In contrast, minor groove binding of the octapeptide SPKKSPKK seems to partially modify the intercalative properties of the acridine moiety of 2. In vitro cytostatic and cytotoxic activities against a murine leukemia cell line (L1210), as well as inhibition of [3H]thymidine incorporation, are reported. Compound 1, which is a better inhibitor of DNA synthesis than 2, is also 2.8-fold more potent in terms of growth inhibition. Both drugs are efficient cytostatic agents, but are weakly cytotoxic. The DNA-binding abilities of the two molecules are well correlated to their biological properties. Thus, DNA can be considered as the primary target for these new ligands.

Amino Acid Sequence↗
PubMed1992

DNA-binding properties of a distamycin-ellipticine hybrid molecule.

We have synthesized a distamycin-ellipticine hybrid compound and investigated its interaction with DNA, using various optical and gel electrophoresis techniques. Binding of the hybrid to DNA is evidenced by spectral shifts, fluorescence quenching, and induced linear dichroism. Absorbance measurements have been used to generate Scatchard plots, which reveal that the interaction cannot be described adequately in terms of a single binding mode, probably because of simultaneous intercalation and minor groove binding of the ligand. Competition with added distamycin has been used to verify involvement of the N-methyl-pyrrole portion of the hybrid molecule in the binding reaction. From electric linear dichroism experiments, it is estimated that the orientation of the DNA-bound ellipticine chromophore in the hybrid differs by about 10 degrees from the orientation of the equivalent chromophore lacking a distamycin tail. Topoisomerase assays establish that binding of the hybrid unwinds the DNA helix by a minimum of 11 degrees, which is consistent with intercalation but notably smaller than the unwinding angle of ellipticine. In footprinting experiments, it is found that the AT- and GC-specificity of distamycin and ellipticine, respectively, appear to be merged in the binding of the hybrid, which produces a pattern of protection distinct from the characteristic patterns for either of the parent compounds. The hybrid is an extremely effective inhibitor of cutting by DNase I.

Chelating Agents↗
PubMed1991

Effect of the amine non-leaving group on the structure and stability of DNA complexes with cis-[Pt(R-NH2)2(NO3)2].

The antitumor compound cis-[Pt(NH3)2Cl2] (cisplatin), conserves two ammine ligands during the reaction with its cellular target DNA. Modifications of these non-leaving groups change the antineoplastic properties of this compound and its genotoxic effects. It is therefore of interest to determine the influence of non-leaving groups on the structure and stability of DNA in vitro. We have investigated platinum-DNA adducts formed by cis-[Pt(R-NH2)2(NO3)2] (where R-NH2 = NH3, methylamine, cyclobutylamine, cyclopentylamine and cyclohexylamine) as a function of DNA binding. All compounds quantitatively reacted with DNA in less than 1 h at 37 degrees C. They formed bifunctional adducts with adjacent nucleotides judging from the displacement of the intercalating molecule ethidium bromide, ultraviolet absorption spectroscopy and circular dichroism. Substitution of a H on the NH3 ligand by alkyl groups dramatically destabilized the platinum-DNA complex. Thermal stability decreased progressively with an increasing number of carbon atoms, delta tm = -4.4 degrees C for 3 cyclohexylamine-platinum-DNA adducts/1000 nucleotides, conditions where cisplatin had no effect. DNA adducts with cyclobutylamine and cyclohexylamine ligands inhibited the hydrolysis of platinum-DNA complexes by S1 nuclease. Km for the digestion of DNA containing these lesions was 2.3 times greater than for cisplatin, indicating steric inhibition of enzyme-substrate complex formation. These results show that the non-leaving groups of substituted cis-Pt(II) compounds may destabilize DNA and interfere with protein-DNA interactions. These perturbations may have consequences for the genotoxic and antitumor activities of platinum compounds.

Antineoplastic Agents↗
PubMed1991

Fibrin sealant improves surgical results of type A acute aortic dissections.

From January 1984 to July 1990, 63 patients were operated on for type A acute aortic dissection. Forty-two patients (aged 22 to 80 years) had isolated replacement of the ascending aorta with the following techniques: group 1 (n = 10) had replacement of the ascending aorta with an intraluminal sutureless graft, group 2 (n = 14) had a Dacron prosthesis sutured to the aorta, and in group 3 (n = 18) the proximal and distal aortic stumps were glued together and reinforced at the suture sites with fibrin sealant before implantation of the Dacron prosthesis. There were no significant differences between the three groups with respect to age, sex, or preoperative clinical and anatomical data. Three (30%) intraoperative deaths occurred in group 1, 4 (29%) in group 2, and none in group 3. Cross-clamp and extracorporeal circulation time were significantly lower in group 1 when compared with groups 2 and 3. Perioperative blood loss during the first 24 hours was significantly lower in group 3 (372 +/- 155 mL) when compared with group 1 (755 +/- 210 mL; p less than 0.05) or group 2 (1,055 +/- 370 mL; p less than 0.01). Total hospital mortality was 7 (70%) in group 1, 6 (43%) in group 2, and 1 (5.5%) in group 3. All patients were reviewed: one late death occurred in group 2 and none in the other groups. All survivors were in good clinical condition. In conclusion, intraluminal sutureless grafts allowed shorter cross-clamp and extracorporeal circulation time but did not improve surgical results for treatment of type A acute aortic dissections.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

[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↗
PubMed1991

[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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

[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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗