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Biomedical subjects

J Marty

Publications and source records attributed to J Marty.

At least 19 recordsLinked to original sources

Amphibian micronucleus test in vivo: evaluation of the genotoxicity of some major polycyclic aromatic hydrocarbons found in a crude oil.

The micronucleus test using erythrocytes of Pleurodeles waltl larvae (Amphibia, Salamandridae) was used to detect the possible genotoxicity of four polycyclic aromatic hydrocarbons (naphthalene, anthracene, phenanthrene and benzo[a]pyrene), which represent a major fraction of crude oil. Larvae were reared in water containing the test compound and the levels of micronucleated red blood cells were compared with those found in larvae reared in control water. The results are compared with published data from other tests used to evaluate the clastogenic or mutagenic properties of compounds. The results obtained confirm that benzo[a]pyrene has a strong genotoxic potential, whereas the genotoxicity of naphthalene is weak; in contrast, anthracene and phenanthrene gave a negative response.

Animals

Aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam.

The effect of aging on the pharmacodynamics of midazolam was investigated in a double-blinded study involving 39 consenting patients ranging in age from 39 to 77 yr. Midazolam was infused intravenously (i.v.) using a pharmacokinetic model-driven drug infusion device to achieve a plasma midazolam concentration that was held constant for the 10-min duration of the study. Blood samples were obtained from the radial artery at 5 and 10 min for subsequent measurement of the plasma midazolam concentrations. With the 10-min sample, the patients were also assessed for the presence or absence of responsiveness to verbal command. To ensure that the pharmacodynamic end-point was assessed under the condition of a relative steady-state effect-site midazolam concentration, only those patients (n = 33) in whom the plasma midazolam concentration at 10 min was within 30% of the measured concentration at 5 min were included in the subsequent data analyses. Logistic regression was used to fit the verbal command response/no response data to a mathematical model that included patient age and the plasma midazolam concentration measured at 10 min. Cp50, the steady-state plasma midazolam concentration at which 50% of patients would be expected not to respond to a specific stimulus (e.g., verbal command), was calculated as a function of age from the parameterized logistic model. The midazolam Cp50 for response to verbal command decreased significantly (P = 0.034) with increasing patient age, demonstrating that aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam independent of pharmacokinetic factors.

Adult

[Coronary patient undergoing non cardiac surgery and Diprivan].

It is legitimate to avoid the administration of propofol in patients suffering from severe ischaemic heart disease (unstable angina). Propofol may be given to patients with stable angina. However, to avoid hypotension, which may compromise oxygen delivery to areas of myocardium supplied by stenosed arteries, it is essential to treat any possible hypovolaemia and to administer fentanyl before tracheal intubation, in order to reduce the dose of propofol.

Anesthesia, Intravenous

[Cesarean section, mitral valve disease and pulmonary hypertension. Implications of hemodynamic monitoring on anesthetic management].

We present the case of a 25-year-old woman with mitral valve disease and severe pulmonary hypertension scheduled for Caesarean section under general anaesthesia. General anaesthesia for such cardiac patients requires usually high doses of fentanyl prior to intubation, which favours maternal inhalation and neonatal ventilatory depression. Invasive haemodynamic monitoring allowed a rapid sequence induction, with an optimal drug titration and an early recovery.

Adult

Role of isradipine and other antihypertensive agents in the treatment of peri- and postoperative hypertension.

The traditional therapy of perioperative hypertension is now being challenged by the availability of new agents. Vasodilator therapy should be the first-line choice, although dihydropyridine calcium antagonists, particularly isradipine, appear to be suitable in this setting because of their pharmacological properties. Because of its ultrashort half-life, sodium nitroprusside has to be administered by continuous infusion, even for the treatment of an acute elevation of blood pressure. This is not the case with the new agents that have longer durations of action. A bolus administration is sufficient for the correction of most elevations of arterial pressure that are due to transient adrenergic activation. Continuous infusion is required only in patients who have sustained increases of systemic vascular resistance; these are usually patients who are already hypertensive.

Adrenergic alpha-Antagonists

Improving morbidity and mortality after cardiac surgery.

Over the past three decades there has been an enormous increase in the number of cardiac operations, particularly on patients with coronary artery disease. Technical advances in cardiac surgery, anaesthesia, monitoring and intensive care would have been expected to reduce morbidity and mortality, but the incidence of complications has, in fact, increased. The increasing use of coronary angiography and the development of interventional cardiology have caused a change in the type of patients scheduled for surgery--they have become progressively older and sicker than in the 1970s. Consequently, the management of patients has to be revised regularly. Careful selection of patients, and the defining of specific strategies for anaesthetic and surgical management are required to improve the outlook for post-surgical complications.

Cardiac Surgical Procedures

Induction and characterization of cytochromes P450IA and -IIB in the newt, Pleurodeles waltl.

The newt (Pleurodeles waltl) is an amphibian species used in a mutagenicity test (micronucleus). This study was carried out to establish if the inducibility of hepatic cytochromes P450 of this species is similar to that of the rat. Our results showed that the newt is characterized by a lower level of hepatic cytochrome P450-dependent activities than the rat. Variations of enzymatic activities according to sex and season were observed. Specific activities in newt were characterized by an almost complete insensitivity to induction by phenobarbital pretreatment. On the other hand, pretreatment by 3-methylcholanthrene resulted in an increase in the metabolism of several hydroxycoumarin and resorufin derivatives, similar to the effects observed in rat liver. Occurrence of specific forms of cytochromes P450 was assessed by specific antibodies.

7-Alkoxycoumarin O-Dealkylase

Coronary and left ventricular hemodynamic responses following reversal of flunitrazepam-induced sedation with flumazenil in patients with coronary artery disease.

The effects of reversal of flunitrazepam-induced sedation with flumazenil on coronary hemodynamics, myocardial oxygen consumption (MVO2), and left ventricular (LV) performance were investigated, in a double-blind trial, in 12 patients with stable coronary artery disease undergoing cardiac catheterization. Coronary sinus blood flow was measured by continuous thermodilution. Arterial and coronary sinus blood were analyzed for oxygen and lactate contents. The determinants of LV performance were obtained from the cardiac output measured by thermodilution and from left heart catheterization data. To reverse flunitrazepam-induced sedation, patients were randomly allocated to receive placebo or flumazenil (by increment, up to 1 mg) at the end of procedure. In the placebo group, no significant hemodynamic changes were observed. In the flumazenil group, heart rate, cardiac index, maximum velocity of shortening, and relaxation time constant were not significantly altered. By contrast, mean aortic pressure and LV end-diastolic pressure (baselines: 90 +/- 5 and 7.3 +/- 4.1 mmHg, respectively) increased (9%, P less than 0.05 and 67%, P less than 0.05, respectively) after flumazenil administration, but these changes represented mainly a return toward presedation values. MVO2 and coronary resistance were not significantly altered, whereas CSBF increased slightly (baseline: 119 +/- 20 ml/min; increase 10%, P less than 0.05). No electrocardiographic evidence of myocardial ischemia was observed during the study. These data show that reversal of benzodiazepine effects with flumazenil is not associated with a major alteration of LV systolic function, relaxation, or coronary hemodynamics in patients with coronary artery disease. Nevertheless, it should be cautiously used when LV end-diastolic pressure is increased at the time of its administration.

Adult

Comparison of sufentanil and fentanyl to supplement N2O-halothane anesthesia for total hip arthroplasty in elderly patients.

Sufentanil was compared with fentanyl as a supplement to nitrous oxide-halothane anesthesia in a double-blind study of 30 elderly patients undergoing total hip arthroplasty. Comparisons were made with respect to (a) hemodynamic (heart rate and blood pressure) and adrenergic (plasma norepinephrine and epinephrine levels) responses during surgery and recovery; (b) time to extubation after the end of surgery; and (c) postoperative analgesia. No difference was observed between the two groups with respect to demographic data, blood gas tensions, or hemodynamic and adrenergic responses to surgery and recovery. Total doses of opioids used were 0.7 +/- 0.3 micrograms/kg of sufentanil and 6 +/- 2.6 micrograms/kg of fentanyl. Times between end of surgery and extubation were not different (60 +/- 54 min in the fentanyl group and 58 +/- 52 min in the sufentanil group). The number of patients needing postoperative analgesia did not differ between the two groups, but use of analgesia was significantly delayed in the sufentanil group (168 +/- 25 vs 127 +/- 29, P less than 0.05). This study suggests that in elderly patients sufentanil confers a greater residual analgesia than fentanyl in the immediate postoperative period.

Adjuvants, Anesthesia

Desensitization of myocardial beta-adrenergic receptors in cirrhotic rats.

Cardiac responses to catecholamines are known to be attenuated in chronic liver disease. To elucidate the role of beta-adrenergic receptor alteration in this phenomenon, we measured heart rate responsiveness to isoprenaline and myocardial beta-adrenergic receptor-binding characteristics in three groups of rats: those that were sham operated, those that had portal vein stenosis and those that were cirrhotic because of bile duct ligation. Responsiveness to isoprenaline was evaluated in conscious rats by the dose of isoprenaline needed to increase basal heart rate by 50 beats/min and by the maximal heart rate response. beta-Receptor characteristics in heart membranes were derived from 125I-iodocyanopindolol binding data. Compared with sham-operated controls, cirrhotic rats needed a significantly higher dose of isoprenaline to raise basal heart rate by 50 beats/min (102.3 +/- 19.1 vs. 28.3 +/- 11.3 ng/kg) and lower maximal heart rate response (104 +/- 29 vs. 158 +/- 61 beats/min). In addition, myocardial beta-receptor density was significantly lower in cirrhotic rats (26.5 +/- 4.6 vs. 37.5 +/- 10.3 fmol/mg protein) and the dissociation constant was higher (31.6 +/- 17.0 vs. 14.0 +/- 2.5 pmol/L). Analysis of beta 1/beta 2 subpopulations revealed that the decreased total beta-receptor density was entirely due to selective beta 1-receptor down-regulation. beta-Receptor affinity for agonist was not altered in cirrhotic rats. Rats with portal vein stenosis showed no significant differences in either isoprenaline responsiveness or beta-receptor characteristics when compared with controls. These results indicate that beta-adrenergic receptor down-regulation may be responsible for the myocardial hyporesponsiveness to catecholamines observed in cirrhosis.

Animals

Does the stress of admission to an intensive care unit influence arginine vasopressin secretion and renal diluting ability?

The pathogenesis of excessive arginine vasopressin (AVP) release and hyponatraemia in euvolaemic intensive care unit (ICU) patients is poorly understood. Stress has frequently been proposed as a possible determinant, but its actual responsibility has not been adequately assessed. Therefore, water-load tests were prospectively performed in 11 patients admitted to the ICU for severe or potentially severe diseases, but who had no other condition which could result in excessive AVP release or impairment of renal diluting ability. Renal diluting ability was normal in 9 patients. Two patients exhibited very slight defects, which might be the consequence of subclinical haemodynamic alterations, since one had a pulmonary embolism and the other manifested a gastrointestinal haemorrhage just after the completion of the water load. Nevertheless, plasma AVP levels decreased in response to the water load in all the patients, resulting in a significant decrease in mean values. Plasma norepinephrine values were found to be elevated both before and after water loading. A highly significant correlation existed between the levels of norepinephrine and those of AVP measured before the load, but was lost after it. In addition, norepinephrine values were markedly elevated in two patients who exhibited strictly normal renal diluting abilities, and no correlation was found between plasma norepinephrine values and any parameter of renal water excretion. Our study shows that the stress of a serious illness and of admission to an ICU does not seem to interfere, by itself, with osmotic regulation of AVP secretion and renal diluting ability, and that sympathetic activation is not, under such circumstances, a predominant stimulus for AVP release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult