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Biomedical subjects

M Bertrand

Publications and source records attributed to M Bertrand.

At least 55 records · Page 3Linked to original sources

[Risk factors for mortality in abdominal aortic surgery].

OBJECTIVE: To analyse pre and peroperative variables for predicting mortality after abdominal aortic surgery. STUDY DESIGN: Prospective study. PATIENTS: We prospectively included 658 consecutive patients undergoing abdominal aortic surgery from January 1993 to July 1997. METHODS: Age, gender, hypertension, history of myocardial infarction or coronary revascularization, angina pectoris, diabetes, arrhythmia, cardiac insufficiency, serum creatinine > 150 mumol.L-1, beta-blockers therapy, calcium channel inhibitors, angiotensin converting enzyme inhibitors were preoperative analysed variable. Type of aortic disease (anuerysms versus aortic occlusion), duration of surgery, blood loss, type of laparotomy (medium versus lombotomy) were peroperative analysed variables. Haemoglobinemia was monitored during surgery and patients were transfused if haemoglobinaemia < 80 g.L-1. RESULTS: Thirty-three patients died after aortic surgery (5%). In multivariate analysis, angina pectoris (OR = 5.47, P < 0.001), chronic obstructive bronchopulmonary disease (OR = 2.27, P = 0.05) and duration of surgery (OR = 1.60, P < 0.001) were the independent predictive factors of mortality. Age, blood loss were predictive factors only in univariate analysis. CONCLUSION: Angina pectoris and COBP were the two independent preoperative factors of mortality. The duration of surgery was the only peroperative factor. Well monitored blood loss was not a predictive factor.

Aged↗

Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling.

A strategy is presented to predict interindividual variation in drug plasma levels in vivo by the use of physiologically based pharmacokinetic modeling and human in vitro metabolic parameters, obtained through the combined use of microsomes containing single cytochrome P450 enzymes and a human liver microsome bank. The strategy, applied to the pharmaceutical compound (N-[2-(7-methoxy-1-naphtyl)-ethyl]acetamide), consists of the following steps: (1) estimation of enzyme kinetic parameters K(m) and V(max) for the key cytochrome P450 enzymes using microsomes containing individual P450 enzymes; (2) scaling-up of the V(max) values for each individual cytochrome P450 involved using the ratio between marker substrate activities obtained from the same microsomes containing single P450 enzymes and a human liver microsome bank; (3) incorporation into a physiologically based pharmacokinetic model. For validation, predicted blood plasma levels and pharmacokinetic parameters were compared to those found in human volunteers: both the absolute plasma levels as well as the range in plasma levels were well predicted. Therefore, the presented strategy appears to be promising with respect to the integration of interindividual differences in metabolism and prediction of the possible impact on plasma and tissue concentrations of drugs in humans.

Acetamides↗

Rapid assessment of drug metabolism in the drug discovery process.

For a few years, in vitro models have been used as part of high-throughput screening (HTS) programs to characterize metabolic stability, drug permeability and drug solubility. This has allowed the rapid selection of lead candidates based not only on pharmacological endpoints but also on biopharmaceutical specifications. What has now become clear is that the huge amount of data produced to sort series of compounds has a limited predictive value when used to predict human pharmacokinetic parameters. More complex in vitro tests together with some simple in vivo tests used as validation steps have been developed in order to provide absolute data that may be used as a complement to lead selection providing reliable predictions not only of human pharmacokinetics but also of potential drug-drug interactions. These models may be used as part of selective drug screening (SDS) programs. Further advances in analytical and in vitro techniques will see some of these models shifting from SDS to HTS programs putting the emphasis on the use of expert systems and physiologically based pharmacokinetic models (PBPK) to provide meaningful endpoint data.

Animals↗

Cardiac troponin I is reliable with immediate but not medium-term cardiac complications after abdominal aortic repair.

BACKGROUND: The diagnosis of cardiac complications is particularly challenging in the postoperative course of non-cardiac surgery. Follow-up of patients suggests that silent or symptomatic postoperative myocardial infarction have similar short-term outcomes. Cardiac troponin I (cTnI) has been reported as being a sensitive and specific marker of these complications. METHODS: We conducted a prospective study to determine the cut-off values of cTnI which may predict cardiac complications, i: in the postoperative period until discharge, and ii: during a 1-year period after aortic surgery. Three hundred and twenty-nine consecutive patients undergoing infrarenal aortic surgery were included over a 2-year period in a single center. cTnI was measured at recovery and on the 1st, 2nd and 3rd postoperative days. The presence or absence of cardiac complications was classified by reviewers who had no knowledge of cTnI. For evaluation of the ideal discrimination value of cTnI between the complicated and uncomplicated patient groups, we calculated receiver-operator characteristics for the mean values of the peak of cTnI. RESULTS: Thirteen patients (4%) developed 19 postoperative cardiac complications. Thirteen patients (4%) died in the postoperative period. Nine patients (3%) developed 10 cardiac complications during the 1-year follow-up in 316 patients. In 280 patients, cTnI was below 0.5 ng/ml, in 22 patients between 0.5 and 1.5 ng/ml and the 27 remaining patients had a cTnI higher than 1.5 ng/ml. The area under the curve for postoperative cardiac complications was 0.84 (SD=0.21). A limit value of 0.54 ng/ml yielded a sensitivity of 75% and a specificity of 89%. The area under the curve for late cardiac complications was 0.45 (SD= 0.13). CONCLUSION: A cTnI level greater than 0.54 ng/ml appears to be correlated with the occurrence of cardiac complications in the period until discharge, but no value of cTnI is predictive of late cardiac complications occurring in the 1st year after aortic surgery.

Aged↗

Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man.

1. In the present study, nine cytochrome P450 enzyme activities in seven species were characterized to allow a practical means of comparing this important metabolic step between various test animals and man. 2. Enzyme activities and kinetic parameters were first determined towards marker substrates for human cytochrome P450 enzymes. Inhibition profiles were then determined with both antibodies directed against various cytochrome P450 enzymes and with chemical inhibitors. 3. Both the enzyme kinetic parameters/enzyme activities, and the inhibition profiles obtained for the animal species were compared with those obtained for human liver microsomes in order to postulate the animal species most similar to man with regard to each individual cytochrome P450 enzyme activity. 4. It was found that, as expected, none of the tested species was similar to man for all the measured P450 enzyme activities, but that in each species only some of the P450 enzyme activities could be considered as similar to man. 5. When it is known which human cytochrome P450 enzymes are involved in the metabolism of a compound, the comparative data presented here can be used for selecting the most suitable species for in vitro and in it no experiments.

Animals↗

Clinical and angiographic results with the ACS MULTI-LINK DUET trade mark Coronary Stent System - the DUET Study.

BACKGROUND: The DUET Study is a multicenter prospective efficacy and safety evaluation of the ACS MULTI-LINK DUET coronary stainless steel balloon-expandable stent. AIMS: The primary objective was to determine the one-month incidence of MACE (major adverse cardiac events). The secondary objectives were the acute success rate, the restenosis and reocclusion rates (assessed by quantitative coronary angiography (QCA)) at six months and the occurrence of MACE in hospital and at six months. METHODS: Two hundred and ten patients were enrolled between February and June 1998 in 18 European centers. Successful stent placement was achieved in 209 patients. All patients were treated with ticlopidine 500 mg/day for one month and with aspirin >/=100 mg/day. To allow the investigators to gain familiarity with the stent system, the first one to three patients per center formed a separate lead-in population leaving an intention-to-treat population of 157 patients. The majority of the intention-to-treat population were male (79%); 28% had unstable angina, 69% had stable angina, 44% had had a previous myocardial infarction, 15% had had a previous percutaneous transluminal coronary angioplasty, and 3% had a history of stroke. The target vessel was 38.5% left anterior descending artery, 20.5% left circumflex artery and 41.0% right coronary artery. RESULTS: All but one of the intention-to-treat patients were effectively stented (17 required multiple stents). Six-month angiographic follow-up was available in 90% of the intention-to-treat population. Minimal lumen diameter (MLD) postprocedure was 2.61 +/- 0.33 mm, with a residual diameter stenosis of 16%. Six-month follow-up data showed an MLD of 1.87 +/- 0.56 mm with a residual diameter stenosis of 36%. The binary restenosis rate (>/=50% residual stenosis) was 15.6%. Up to one month following the procedure 94.9% of the population was MACE-free, with two subacute occlusions. At six months all patients were alive, of whom 82.8% were MACE-free, and 73% were free of anginal complaints. CONCLUSION: The results observed in the current DUET registry are comparable to data of other balloon-expandable-stent trials, with a low incidence of clinical events at follow-up.

Journal Article↗

Spectroscopic properties of protochlorophyllide analyzed in situ in the course of etiolation and in illuminated leaves.

The spectroscopic properties of photoactive (i.e. flash-transformable) and nonphotoactive protochlorophyll(ide)s (Pchl(ide)) were reinvestigated during the development of bean leaves in darkness. Two phases in the process of Pchl(ide) accumulation were apparent from quantitative measurements of pigment content: a lag phase (first week) during which photoactive Pchl(ide) accumulated faster than nonphotoactive Pchl(ide); and a fast phase (second week), showing parallel accumulation of both types of Pchl(ide). 'Flashed-minus-dark' absorbance difference spectra recorded in situ at 77 K showed that P650-655 was the predominant form of photoactive protochlorophyllide regardless of developmental stage. Quantitative analysis of energy migration processes between the Pchl(ide) forms showed the existence of energy transfer units containing a 1:8 ratio of nonphotoactive and photoactive Pchl(ide)s during development. Gaussian deconvolution of in situ 77 K fluorescence spectra indicated that the 633 nm band of nonphotoactive Pchl(ide) was made of four bands, at 625, 631, 637 and 643 nm, whose relative amplitudes only slightly changed during development. The emission band of photoactive Pchlide was also analyzed using the same method. Three components were found at 644, 652 and 657 nm. The emission band of P650-655 included the last two components, which become predominant only in fully etiolated plants. Photoactive Pchlide with an emission maximum at 653 nm was detected in the light during development of leaves of photoperiodically grown plants.

Darkness↗

Photoactive protochlorophyllide regeneration in cotyledons and leaves from higher plants.

Chlorophyll accumulation during greening implies the continuous transformation of photoactive protochlorophyllide (Pchlide) to chlorophyllide. Since this reaction is a light-dependent step, the study of regeneration of photoactive Pchlide under a continuous illumination is difficult. Therefore this process is best studied on etiolated plants during a period of darkness following the initial photoreduction of photoactive Pchlide. In this study, the regeneration process has been studied using spinach cotyledons, as well as barley and bean leaves, illuminated by a single saturating flash. The regeneration was characterized using 77 K fluorescence emission and excitation spectra and high-performance liquid chromatography. The fluorescence data indicated that the same spectral forms of photoactive Pchlide are regenerated by different pathways: (1) photoactive Pchlide regeneration starts immediately after the photoreduction through the formation of a nonphotoactive Pchlide form, emitting fluorescence at approximately 651 nm. This form is similar to the large aggregate of photoactive Pchlide present before the illumination, but it contains oxidized form of nicotinamide adenine dinucleotide phosphate, instead of the reduced form (NADPH), in the ternary complexes; and (2) after the dislocation of the large aggregates of chlorophyllide-light-dependent NADPH:Pchlide a photooxidoreductase-NADPH ternary complexes, the regeneration occurs at the expense of the several nonphotoactive Pchlide spectral forms present before the illumination.

Cotyledon↗

[Endovascular treatment of aorto-iliac aneurysms. Made-to-measure endoprotheses increase the feasibility].

The authors describe their experience of tailoring endoprostheses for endovascular treatment of aorto-iliac aneurysms with components available on the market. Between January 1996 and December 1999, 188 aorto-iliac aneurysms were treated by tailor-made endoprostheses using self-expanding Z stents made of stainless steel compiled with polyester ligatures and covered with standard commercially available polyester prostheses. These endoprostheses were implanted with an 18 to 24 Fr (usually 20 Fr) introducer and positioned by a surgical approach. This method allows construction of tubular, bifurcated, digressive or occlusive endoprostheses associated with an extra-anatomical bypass graft. It increased the number of endovascular procedures for aorto-iliac aneurysms in the authors' department. This number has been further increased by using endoprostheses with an uncovered proximal or distal stent for cases with particularly short or angled necks and by using hybrid endoprostheses with one or more extremities without a stent, allowing surgical suture of the anastomosis. The authors' results show that tailoring endoprostheses considerably increased the feasibility of endovascular treatment of aorto-iliac aneurysms, even in unselected patients whilst providing an effectiveness and safety to justify the continuation of this experience.

Aortic Aneurysm, Abdominal↗

Study of catheter designs and drug mixing processes using 2D steady numerical simulations.

The effectiveness of substance delivery through catheters is an important issue in interventional radiology, especially for infusion therapies where the pharmacokinetic advantage of local intra-arterial drug administration has been firmly established. In principle, the procedure is used to provide appropriate local concentrations while maintaining low systemic values so as to minimise the global effect and toxicity of the intervention. However, poor drug mixing may produce excessive local concentrations potentially damaging for the surrounding tissues and may lead to unsuccessful therapies. These phenomena have been observed in the infusion therapies of liver cancers through the hepatic artery and with brain tumour therapies through the carotid artery. Many aspects of the drug delivery methodology have been explored in order to determine the infusion conditions that would provide optimal mixing: the catheter tip design is considered one of the most important characteristics to be investigated for this purpose. Interestingly, it turns out that angiographic procedures could also benefit from this, because better mixing properties are associated with designs that provide potentially less harmful flow conditions such as jets, whipping and recoil of the catheter on the vascular wall. A 2D steady numerical model is proposed, to simulate the main physical processes occurring during catheter substance infusion: blood dynamics is taken into account with the Navier-Stokes equations and substance dispersion by the flowing blood with the advection-diffusion equation. The model is used to evaluate mixing properties of certain catheter designs in different flow conditions. In particular, two types of side hole catheter are compared in the context of water bath injection and in the context of vessel injection. The simulations suggest that the improved mixing reported with water bath experiments would not be maintained in the clinical context of arterial circulation.

Catheterization↗

A system-based approach to modeling the ultrasound signal backscattered by red blood cells.

A system-based model is proposed to describe and simulate the ultrasound signal backscattered by red blood cells (RBCs). The model is that of a space-invariant linear system that takes into consideration important biological tissue stochastic scattering properties as well as the characteristics of the ultrasound system. The formation of the ultrasound signal is described by a convolution integral involving a transducer transfer function, a scatterer prototype function, and a function representing the spatial arrangement of the scatterers. The RBCs are modeled as nonaggregating spherical scatterers, and the spatial distribution of the RBCs is determined using the Percus-Yevick packing factor. Computer simulations of the model are used to study the power backscattered by RBCs as a function of the hematocrit, the volume of the scatterers, and the frequency of the incident wave (2-500 MHz). Good agreement is obtained between the simulations and theoretical and experimental data for both Rayleigh and non-Rayleigh scattering conditions. In addition to these results, the renewal process theory is proposed to model the spatial arrangement of the scatterers. The study demonstrates that the system-based model is capable of accurately predicting important characteristics of the ultrasound signal backscattered by blood. The model is simple and flexible, and it appears to be superior to previous one- and two-dimensional simulation studies.

Computational Biology↗

Does desflurane alter left ventricular function when used to control surgical stimulation during aortic surgery?

BACKGROUND: Although desflurane is commonly used to control surgically induced hypertension, its effects on left ventricular (LV) function have not been investigated in this clinical situation. The purpose of the present study was to evaluate the LV function response to desflurane, when used to control intraoperative hypertension. METHODS: In 50 patients, scheduled for vascular surgery, anesthesia was induced with sufentanil 0.5 microg/kg, midazolam 0.3 mg/kg and atracurium 0.5 mg/kg. After tracheal intubation, anesthesia was maintained with increments of drugs with controlled ventilation (N2O/O2=60/40%) until the start of surgery. A 5 Mhz transesophageal echocardiography (TEE) probe was inserted after intubation. Pulmonary artery catheter and TEE measurements were obtained after induction (to)(control value), at surgical incision (t1) if it was associated with an increase in systolic arterial pressure (SAP) greater than 140 mmHg (hypertension) and after control of hemodynamic parameters by administration of desflurane (return of systolic arterial pressure to within 20% of the control value) (t2) in a fresh gas flow of 31/ min. RESULTS: Sixteen patients developed hypertension at surgical incision. SAP was controlled by desflurane in all 16 patients. Afterload assessed by systemic vascular resistance index (SVRI), end-systolic wall-stress (ESWS) and left-ventricular stroke work index (LVSWI) increased with incision until the hypertension returned to post-induction values with mean end-tidal concentration of 5.1+/-0.7% desflurane. No change in heart rate, cardiac index, mean pulmonary arterial pressure, stroke volume, end-diastolic and end-systolic cross-sectional areas, fractional area change and left ventricular circumferential fiber shortening was noted when desflurane was added to restore blood pressure. CONCLUSION: This study demonstrates that in patients at risk for cardiac morbidity undergoing vascular surgery, desflurane is effective to control intraoperative hypertension without fear of major cardiac depressant effect.

Anesthetics, Inhalation↗

Introduction

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Journal Article↗

Treatment of intraoperative refractory hypotension with terlipressin in patients chronically treated with an antagonist of the renin-angiotensin system.

UNLABELLED: The goal of the present study was to determine whether terlipressin, an agonist of the vasopressin system, could counteract perioperative hypotension refractory to common vasopressor therapy and to analyze its circulatory effects. We enrolled 51 consecutive vascular surgical patients chronically treated with angiotensin-converting enzyme inhibitors or antagonists of the receptor of angiotensin II, who received a standardized opioid-propofol anesthetic. Of these 51 patients, 32 had at least one episode of hypotension, which responded to epinephrine or phenylephrine. In 10 other patients, systolic arterial pressure (SAP) did not remain above 100 mm Hg for 1 min, despite three bolus doses of ephedrine or phenylephrine. In these patients, we injected a bolus of 1 mg of terlipressin, repeated twice if necessary. Hemodynamic and echocardiographic variables were recorded every 30 s over 6 min. In eight patients, arterial pressure was restored with one injection of terlipressin; in two other patients, three injections were necessary. One minute after the last injection of terlipressin, the SAP increased from 88+/-3 to 100+/-4 mm Hg and reached 117+/-5 mm Hg (P = 0.001) 3 min after the injection and remained stable around this value. This increase in SAP was associated with significant changes in left ventricular end-diastolic area (17.9+/-2 vs 20.2+/-2.2 cm2; P = 0.003), end-systolic area (8.1+/-1.3 vs 9.6+/-1.5 cm2; P = 0.004), end-systolic wall stress (45+/-8 vs 66+/-12; P = 0.001), and heart rate (60+/-4 vs 55+/-3 bpm; P = 0.001). Fractional area change and velocity of fiber shortening did not change significantly. No additional injection of vasopressor was required during the perioperative period. No change in ST segment was observed after the injection. IMPLICATIONS: Terlipressin is effective to rapidly correct refractory hypotension in patients chronically treated with antagonists of the renin-angiotensin system without impairing left ventricular function.

Aged↗

The hemodynamic effects of anesthetic induction in vascular surgical patients chronically treated with angiotensin II receptor antagonists.

UNLABELLED: The use of angiotensin II receptor subtype-1 antagonists (ARA), recently introduced as antihypertensive drugs, is becoming more prevalent. We studied the prevalence and severity of hypotension after the induction of general anesthesia in 12 patients treated with ARA until the morning of surgery. The hemodynamic response to induction was compared with that of patients treated with beta-adrenergic blockers (BB) and/or calcium channel blockers (CB) (BB/CB group, n = 45) and angiotensin-converting enzyme inhibitors (ACEI) (ACEI group, n = 27). A standardized anesthesia induction protocol was followed for all patients. Hypotension occurred significantly (p < or = 0.05) more often in ARA-treated patients (12 of 12) compared with BB/CB-treated patients (27 of 45) or with ACEI-treated patients (18 of 27). There was a significantly (P < or = 0.001) increased ephedrine requirement in the ARA group (21+/-3 mg) compared with the BB/CB group (10+/-6 mg) or the ACEI group (7+/-4 mg). Hypotension refractory to repeated ephedrine or phenylephrine administration occurred significantly (P < or = 0.05) more in the ARA group (4 of 12) compared with the BB/CB group (0 of 45) or the ACEI group (1 of 27), but it was treated successfully by using a vasopressin system agonist. Treatment with angiotensin II antagonism until the day of surgery is associated with severe hypotension after the induction of anesthesia, which, in some cases, can only be treated with an agonist of the vasopressin system. IMPLICATIONS: Hypotensive episodes occur more frequently after anesthetic induction in patients receiving Angiotensin II receptor subtype-1 antagonists under anesthesia than with other hypotensive drugs. They are less responsive to the vasopressors ephedrine and phenylephrine. The use of a vasopressin system agonist was effective in restoring blood pressure when hypotension was refractory to conventional therapy.

Adrenergic beta-Antagonists↗

Lagrangian speckle model and tissue-motion estimation--theory.

It is known that when a tissue is subjected to movements such as rotation, shearing, scaling, etc., changes in speckle patterns that result act as a noise source, often responsible for most of the displacement-estimate variance. From a modeling point of view, these changes can be thought of as resulting from two mechanisms: one is the motion of the speckles and the other, the alterations of their morphology. In this paper, we propose a new tissue-motion estimator to counteract these speckle decorrelation effects. The estimator is based on a Lagrangian description of the speckle motion. This description allows us to follow local characteristics of the speckle field as if they were a material property. This method leads to an analytical description of the decorrelation in a way which enables the derivation of an appropriate inverse filter for speckle restoration. The filter is appropriate for linear geometrical transformation of the scattering function (LT), i.e., a constant-strain region of interest (ROI). As the LT itself is a parameter of the filter, a tissue-motion estimator can be formulated as a nonlinear minimization problem, seeking the best match between the pre-tissue-motion image and a restored-speckle post-motion image. The method is tested, using simulated radio-frequency (RF) images of tissue undergoing axial shear.

Biomechanical Phenomena↗

[To go along with life until death].

We are faced with difficult and complex questions that cannot be answered by stating great principles or ideological convictions, because they refer to painful situations, always singular, in which each individual, in a unique way, faces his life and his death. But the debate can draw on shared convictions and values. Thus, before being a way of assuming death, the Christian faith is fundamentally a way of welcoming the life, in all times and in its fullness, that Christ has given us. The whole Bible and in particular the ministry of Jesus bear witness to that fight for life, against the scandal of suffering and the powers of death that are a denial of the good work of God. Suffering is never, as such, acceptable or justifiable, and truth is never to surrender to it, as if it was a meaningful destiny. And so all suffering that can be avoided must be so. Regarding death, it is often held back in the margins of our lives and societies, as if it was a sort of setback for our human abilities and especially for medicine. Of course those abilities exist but death is not an illness. It's the natural mark of our human finiteness and there is a time when caring is not intended to cure, but to make up for life that defaults, alleviate suffering. That is why what is called to-day palliative caring is so important. Because even when medicine is powerless in front of illness, it can still do something for the sick. Because of all that, the believer can only be opposed to euthanasia which is, after all, only the exact replica of the useless prolongation of life by medical means it pretends to oppose. It's the same activism, the same pretense, the Bible fights, through which human beings want to remain the masters of life and death. But death is not given, except in deathly violence. As life, it is welcomed and is accompanied. The end of a life is still life. To die is to the live to one's last breath. And that questions the claim to die "with dignity" when life can no more be lived in a "dignified way". But what "dignity" are we talking about? To-day, do we not mistake it with the image of the modern individual, master of himself and a match for the world, assured of his physical strength and of his conscientiousness enabling him to consent. As if the image of dignity was always the same, at every age, for all types of illness or simply of existence. When that image of dignity gets shaky, one discovers sorts of dignity that do not answer those criteria, but that testify that any "body" can be a subject, and that we know nothing about it. Lastly, no law or moral authority, be they lax or restrictive, can suppress compassion, nor the ethical responsibility of the patient, of the doctors, of the family circle. None can take the place of the common requirement: go along with life up to death.

Attitude to Death↗