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D Claude

Publications and source records attributed to D Claude.

13 recordsLinked to original sources
PubMed2004

Aminoglycoside nephrotoxicity.

The main constraints to the administration of aminoglycosides (AG) are risks of nephrotoxicity and ototoxicity, which can lead to renal and vestibular failure. AG accumulation in the kidney may be related to the dosing schedule. As a result, administration of larger doses on a less frequent basis may reduce the drug accumulation in the renal cortex. Many methods have been proposed to reduce AG nephrotoxicity. (1) Molecular modeling and analog synthesis could lead to intrinsically less toxic AG but this approach is time consuming and expensive. Protective approaches such as the co-administration of polyaspartic acid or defferoxamine appear to be very promising in clinical practice. (2) Population pharmacokinetic computer programs, used to control AG serum concentrations, are correct predictors of efficacy but the estimated concentrations in the second compartment are not reliable predictors of nephrotoxicity because they do not take into account non-linear processes such as the AG uptake in the renal cortex or the tubuloglomerular feedback. (3) Finally, modelling the AG nephrotoxicity with probabilistic approaches and/or with deterministic approaches seems to be very promising. These two approaches appear to be not competitive but very complementary in clinical practice. The probabilistic model can be used to predict nephrotoxicity at the beginning the treatment. The deterministic model can be used to simulate and control nephrotoxicity when it is already unfolding and the treatment must be given for a long period of time.

Aminoglycosides↗
PubMed2003

[PK/PD modeling of aminoglycoside nephrotoxicity].

Aminoglycosides are bactericidial antibiotics with a serum concentration-dependent activity. They are mainly eliminated by the kidneys and the main difficulty arising in clinical use is their uptake by the renal cortex which leads to nephrotoxicity. An ototoxicity is also reported. We propose a PK/PD modelling of aminoglycoside nephrotoxicity which unifies more fourty years of physiological knowledge. This deterministic model successively describes the pharmacokinetics of aminoglycosides, their storage into renal cortex, their effect on renal cells, their consequences on the renal function through tubuloglomerular feedback and the changes in the serum concentrations of creatinine that is considered as a toxicity marker. The simulation of the model displays the leading effect of the shape and daily-time of administration schedule on the search for minimizing toxicity.

Amikacin↗
PubMed2001

An illuminative example of nonlinear identification.

The parameter identification of a nonlinear system is often difficult to handle. Through the study of a particular nonlinear system with a limit cycle, corresponding to a biological system with an endogenous rhythm, we show that it is useful to take into account additional algebraic or geometric features of the system to achieve parameter identification.

Homeostasis↗
PubMed2001

Mathematical model of FSH-induced cAMP production in ovarian follicles.

During the terminal part of their development, ovarian follicles become totally dependent on gonadotropin supply to pursue their growth and maturation. Both gonadotropins, follicle-stimulating hormone (FSH) and luteining hormone (LH), operate mainly through stimulatory G protein-coupled receptors, their signal being transduced by the activation of the enzyme adenylyl cyclase and the production of second-messenger cAMP. In this paper, we develop a mathematical model of the dynamics of the coupling between FSH receptor stimulation and cAMP synthesis. This model takes the form of a set of nonlinear, ordinary differential equations that describe the changes in the different states of FSH receptors (free, bound, phosphorylated, and internalized), coupling efficiency (activated adenylyl cyclase), and cAMP response. Classical analysis shows that, in the case of constant FSH signal input, the system converges to a unique, stable equilibrium state, whose properties are here investigated. The system also appears to be robust to nonconstant input. Particular attention is given to the influence of biologically relevant parameters on cAMP dynamics.

Algorithms↗
PubMed2000

Period shift induction by intermittent stimulation in a Drosophila model of PER protein oscillations.

PER protein circadian oscillations in Drosophila have been described by Goldbeter according to a five-dimensional model that includes the possibility of genetic mutation described by changing one parameter, the maximum degradation rate of the PER protein. Assuming that, in a mutant Drosophila this parameter is unreachable, we modify another parameter, the translation rate between the mRNA and the nonphosphorylated form of PER protein, by periodic intermittent activation or inhibition. We show how such a modification, simulated in the model by a periodic, on/off, piecewise constant stimulation (which increases or decreases this parameter) allows the entrainment of oscillations exactly at, or close to, a desired period. In a different context, this suggests that some diseases may be corrected using pharmacological agents according to specific periodic delivery schedules.

Animals↗
PubMed1994

Nonlinear adaptive control of adrenal-postpituitary imbalances and identifiability analysis.

Adrenal-postpituitary imbalances express pathological evolutions of the nonlinear biological oscillator due to hormonal coupling between adrenocortical hormones and vasopressin. This system, based on agonistic-antagonistic equilibration, can be represented by a nonlinear model to be controlled in the pathological case, in order to reach a physiological state. The modeling introduced by E. Bernard-Weil has already led to efficient therapeutics and can thus be considered realistic. We can therefore use the simulated data given by Bernard-Weil, and although our results on control are obtained by simulation, they are meaningful. The therapy is based on the idea of moving the pathological controlled system from the pathological state to the physiological one. However, it is proved that with a periodic control one is not able to achieve the precise objective. This leads us to introduce the locking concept, which allows system parameters to change and provides the basis for an adaptive and iterative control, here given by a sequence of polynomial correctors. In a few iterations we are now able to find the physiological behavior again. Moreover, as we have to identify the parameters of the considered models and control laws, we have to study their structural identifiability. We can prove, thanks to the work of Vajda and his colleagues, the global identifiability of the uncontrolled 12-parameter model. We also prove the local identifiability of the eight-parameter controllers.

Animals↗
PubMed1987

[Physiopathological approach to pathological hyperlactatemia in the diabetic patient. Value of blood metformin].

Type B lactic acidosis, or pathological hyperlactatemia (PHL), is defined by an arterial lactate level greater than 5 mmol X l-1. It is a known and severe complication of diabetes mellitus treated with biguanide hypoglycaemic agents, particularly phenformin which was taken off the French pharmaceutical market in 1977. Metformin, which remains the only biguanide hypoglycaemic agent currently prescribed in France, may also lead to this complication. However it does so less frequently and mostly in the diabetic presenting with renal failure. A few well studied cases showed that PHL could be correlated with excessive metformin blood levels, i.e. a toxic mechanism. In order to find out whether this toxic mechanism was the real cause of PHL in diabetics treated with metformin, a systematic study of metformin blood levels was carried out in 20 such patients. They had all been admitted to a critical care unit presenting with PHL. The results of this study led us to distinguish between two groups of patients. The seven patients of the first group had high metformin blood levels (4.3 to 65.8 micrograms X l-1). In these, renal excretion or extrarenal dialysis lowered or normalized their hyperlactatemia, and six of the seven recovered from PHL. In the second group, with thirteen patients, metformin blood levels were within the normal therapeutic range (0.225 to 3 micrograms X l-1) for seven patients and close to zero for the other six. This second group received the same treatment as the first one. Only three patients recovered, the others all died.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Lactic↗
PubMed1985

[Acute choriocapillaris occlusion in pregnancy and puerperium. Toxemias, thrombotic microangiopathies].

Six cases of gravidic toxemia (4) and thrombotic thrombocytopenic purpura (Moschowitz's disease) in puerperium with choriocapillaris occlusion, were examined. At the acute stage, the vision is improved, ophthalmoscopy of the fundus revealed cystlike bullous exudative subretinal with retinal detachment, yellowish spots (of retinal pigment epithelium) and often minimal localized arteriolar narrowing. The evolution included retina application pigmentary disturbances and Elschnig's spots. Fluorescein angiography showed delayed filling of the capillaris and dye leakage in the subretinal space (first hypofluorescence and late hyperfluorescence). There are various stages of ischaemic involvement but in all cases visual symptoms may be due to central obstructive choroidopathy with delayed filling and occlusion. The retinal detachment in toxemia or Moschowitz disease in pregnancy in secondary to microcirculatory choroidal damage (short ciliary vessels essentially) with rupture of blood retinal barrier. Other constatations are made in disseminated intravascular coagulation, periarteritis nodosa, accelerated nephrosclerosis, hemolytic uremic syndrome in puerperium, and these suggested possible relationship between the various conditions.

Choroid↗
PubMed1984

[Acute edema of the lung in eclampsia].

In 6 cases of eclampsia in the course of pre and post-partum, we could observe neurological disorders associated with acute pulmonary oedema with acute respiratory distress occurring 5 to 72 hours after the first convulsive crisis. Hemodynamic check-up provided various results: 3 cases corresponded to A.P.O resulting from a lesion, with normal capillary pressure. In 3 other cases, there was hemodynamic oedema (overloading with high flow and hypervolemia in one case, myocardial incompetence with hypovolemia in an other case revealed by test filling in a third case). There were clinical signs of left ventricular failure in 4 case. Post-mortem investigations (5 cases) revealed unimportant ultrastructural alterations of myocardium only in 2 cases. Pulmonary histopathological investigations (5 cases) were the investigations carried out in case of oedema resulting from lesions with interstitial and alveolar oedema, hyaline membranes, alteration of pneumocytes, and intra-capillary thrombi. Mendelson's syndrome which was always discussed could be eliminated. The syndrome of respiratory distress was certainly connected with more or less generalized microcirculatory disorders (microembolism with hyperpermeability) connected with hemostasis disorders and cerebral manifestations.

Acute Disease↗
PubMed1981

[Air embolus after Caesarean section (author's transl)].

This is case history of a primigravid woman on whom Caesarean section was carried out in normal conditions for fetal distress, the patient being placed in Trendelenburg position. After the abdomen had been closed there was a sudden collapse with cyanosis, right bundle branch block and then coma with hypertonicity, hyperreflexia and transitory hemiplegia. The only possible diagnosis that could be made was of air embolus following Caesarean section in the light of many investigations that were carried out and the improvement under hyperbaric oxygen treatment and the very irregular progress of the neurological symptoms. Published case histories are rare [12] (published by Walrop, 1953 and Nelson 1960) and over all the result has been unfavourable. The diagnosis can be proven when gas has been found in the blood vessels at autopsy or by the finding of certain clinical signs which indicate the presence of air in the heart or in the blood vessels (water mill sound and the sound of air in the blood vessels). Diagnosis is made by exclusion. The differential diagnosis must be made with amniotic fluid embolus and the other cerebro-vascular accidents, as well as obstetrical shock. The principal factors that bring about air embolus are the entry of air into the dilated uterine veins which is helped by the negative pressure achieved by the Trendelenburg position. As soon as this diagnosis is made it is important to start hyperbaric oxygen treatment and symptomatic resuscitation.

Adult↗