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Biomedical subjects

B Bonnemain

Publications and source records attributed to B Bonnemain.

At least 55 records · Page 3Linked to original sources
PubMed1994

Iodinated contrast media-induced nephropathy: pathophysiology, clinical aspects and prevention.

Administration of iodinated contrast media (CM) for radiographic purposes is a preoccupying cause of acute renal failure. This review of the literature deals with what is known about physiopathology, clinical course, risk factors and prevention. Factors involved in the pathophysiology of CM-induced acute renal failure are vasoconstriction, direct tubular cell injury and tubular obstruction by casts. In the case of pre-existing renal hypoperfusion, CM may disturb the complex interaction between factors which modulate renal haemodynamics by increasing vasoconstrictor factors, notably endothelin peptides. The renal medulla, a zone characterized by a high metabolic activity and a low oxygen tension, may be a specific target for CM-induced effects. CM-induced nephropathy (CMN) is essentially observed in patients with one or more associated risk factors (chronic renal failure, dehydration, diabetes mellitus with impaired renal function, multiple myeloma, large CM volume, intra-arterial rather than intravenous route, etc). There is much debate as to whether newer low osmolar CM (LOCM) are better tolerated than conventional high osmolar CM (HOCM). Most of the animal studies clearly demonstrate the advantages of LOCM over HOCM. Clinical literature is far more confusing, although some recent studies and one meta-analysis demonstrate that LOCM are better tolerated in patients with impaired renal function. The low number of comparative clinical trials carried out in high risk patients, wide variability in CMN definitions, limited number of patients enrolled and inadequacy of various selected endpoints may explain difficulties experienced in demonstrating this advantage. Furthermore, while hydration is correctly maintained during clinical trials, this is not always true in clinical practice. Such a discrepancy could lead to underestimation of the potential advantage of LOCM over HOCM. Effective prevention should associate the correct hydration of patients, identification and, when possible, optimal correction of risk factors, avoidance of repeated CM injections within a short period of time and temporary disruption of treatment with other nephrotoxic drugs (non steroidal antiinflammatory drugs, aminoglycosides, etc).

Acute Kidney Injury↗
PubMed1994

[Contrast products in magnetic resonance imaging].

Contrast agents MRI (Magnetic Resonance Imaging) have been developed to improve the diagnostic information obtained by this technic. They mainly interact on T1 and T2 parameters and increase consequently normal to abnormal tissues contrast. The paramagnetic agents which mainly act on longitudinal relaxation rate (T1) are gadolinium complexes for which stability is the main parameter to avoid any release of free gadolinium. The superparamagnetic agents that decrease signal intensity by an effect on transversal relaxation rate (T2) are developed for liver, digestive and lymph node imaging. Many area of research are now opened for optimal use of present and future contrast agents in MRI.

Contrast Media↗
PubMed1994

Isolated Richter's syndrome of the brain: two recent cases.

Two new cases of central nervous system (CNS) large cell lymphoma without evidence of systemic lymphoma in patients with chronic lymphocytic leukaemia (CLL) are reported. This unusual presentation of Richter's syndrome emphasizes the necessity to evoke this diagnosis in the case of neurologic symptoms in CLL.

Aged↗
PubMed1993

Modulation of the renal effects of contrast media by endothelium-derived nitric oxide in the rat.

RATIONALE AND OBJECTIVES: A possible involvement of endothelium derived relaxing nitric oxide (NO) in the pathogenesis of iodinated contrast media (CM)-induced nephrotoxicity was investigated in the rat. METHODS: Male rats (6 to 12 per group) were uninephrectomized. Six days later, the aorta was clamped above the renal artery and a low-osmolar contrast medium (CM), ioxaglate, was injected (1 mL/min; 3 minutes) via an aortic puncture in the single remaining kidney. Contrast medium was injected with or without the NO-synthase inhibitor L-NAME (100 mg/kg intravenously [i.v.] 5 minutes before CM). One group received L-Arginine, the physiological precursor of NO (100 mg/kg i.v.), 5 minutes before L-NAME. Phenylephrine (300 micrograms/kg; 30 min) was used as a vasoconstrictive NO-independent control. The effects of iohexol, another low-osmolar CM, on creatinine clearance (CrCl) were also studied with and without pretreatment with L-NAME. A control group was subjected to a 3-minute renal ischemia only. Creatinine clearance and urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion were determined before, and 24 and 48 hours after CM administration. Blinded histologic analysis was carried out after completion of the study. RESULTS: When administered alone, neither L-NAME nor L-arginine modified CrCl. Ioxaglate mildly but significantly decreased CrCl at 24 hours (-26.5% of preinjection value). This was similar to the effect observed in the control group subjected to ischemia only. When associated with L-NAME, ioxaglate markedly decreased CrCl (-58 + 11% at 24 hours, P < .05 vs. ioxaglate alone). A similar interaction was noted in the case of iohexol. L-NAME also markedly increased ioxaglate-induced urinary NAG excretion. Phenylephrine had a similar impact on renal function. L-arginine pretreatment reduced the increase in serum creatinine induced by L-NAME+ioxaglate (68 + 17 mumol/L vs. 175 + 59 mumol/L for L-NAME+ioxaglate; P < .05) and urinary NAG excretion. Ioxaglate alone induced only tubular epithelial vacuolization. When associated with L-NAME, this CM induced tubular and vascular lesions, as well as necrosis in the outer medulla. Such histologic effects were clearly inhibited by L-arginine. CONCLUSION: These data indicate that L-NAME, a specific inhibitor of NO-synthase, and phenylephrine, accentuate the nephrotoxicity of CM in the rat. This is consistent with results from the literature showing that CM-toxicity is enhanced by renal ischemia.

Acetylglucosaminidase↗
PubMed1992

[Balanced facial hydrophilicity of ioversol: a qualitative approach of hydrophilicity].

Chimiotoxicity of iodinated contrast media is essentially due to non specific hydrophobic interactions with biologic proteins and membranes. These hydrophobic interactions depend both on the whole molecular lipophilicity and on the spatial accessibility of lipophilic molecular areas. Measurements of lipophilicity by partition coefficient, partially take into account the spatial localisation of hydrophilic groups around the lipophilic area due to the 1,3,5-triiodo-benzene. These measurements have to be completed by an accurate knowledge of the three-dimensional localisation of hydrophilic groups to improve the biocompatibility of polyiodinated contrast media. The concept of evenly distributed facial hydrophilicity aims to minimize the accessibility to lipophilic area by a localisation of hydrophilic group on each plan of the benzene ring. The molecular structure of ioversol allows to put this concept in concrete form thanks to a tertiary anilide group which imposes on one hydroxy group to be located on each face of the 1,3,5-triiodo-benzene ring, providing facial hydrophilic protection.

Contrast Media↗
PubMed1990

Gd-DOTA. Pharmacokinetics and tolerability after intravenous injection into healthy volunteers.

The pharmacokinetics of Gd-DOTA meglumine in humans were evaluated in six healthy male volunteers. The agent was injected intravenously at 0.1 mmol/kg over approximately 2 minutes. Its behavior was found to be similar to that of urographic and angiographic iodinated contrast media with a plasma elimination half-life of 91 +/- 14 minutes (mean +/- standard deviation [SD]), a small distribution volume of 171.0 +/- 19.7 mL/kg and rapid urinary excretion. The results suggest rapid passive extravascular diffusion of gadolinium (Gd)-DOTA in the interstitial space without intracellular penetration, followed by a rapid urinary excretion via glomerular filtration. Furthermore, the results are consistent with animal data that showed that the compound does not cross the normal blood brain barrier. Its plasma pharmacokinetics appeared to be similar to those reported for Gd-DTPA. No relevant biological effects were seen with Gd-DOTA, especially in regard to serum iron and bilirubin levels.

Adult↗
PubMed1989

Hemodynamic and electrophysiologic effects of low osmolar contrast agents during coronary angiography in the dog and the rabbit.

The electrophysiological tolerability of ioxaglate (160 mgI/ml) and iohexol (140 mgI/ml) was assessed in rabbits (n = 12 per group). There was a significant induction of ventricular fibrillation in the group given iohexol. An explanation for this phenomenon could be the lack of sodium in this preparation. Ioxaglate, iopamidol and iohexol (all at 320 mgI/ml) were also compared during coronary angiography in the dog (n = 10) after bolus administration, using the carotid approach (5 and 8 ml-0.5 ml/sec). Each dog received all the compounds in the left coronary artery and selectively in the left anterior descending artery, at random. Four dogs had lethal ventricular fibrillations after iohexol. Iopamidol and iohexol induced significant bradycardia in comparison with saline. A biphasic effect on myocardial contractility was observed with all contrast media: a short-lasting, typical decrease in dP/dt was seen with ioxaglate by the end of injection, while iohexol and iopamidol caused a similar negative inotropic effect in some cases (25%) after increasing dP/dt. The positive inotropic effect was greater with iopamidol and iohexol than with ioxaglate (p less than 0.05). The possible clinical consequences of the lack of sodium in contrast media preparations and of the changes in myocardial function are discussed in the light of the present results.

Animals↗
PubMed1988

Tolerability of hypertonic and isotonic contrast media injected intravenously. A comparative study in the dog.

We examined the use of isotonic and hypertonic contrast media injected intravenously in the dog from the standpoint of cardiovascular tolerance after right atrial injections performed at 2.56 and 5.12 g I/second. The parameters measured were lead II of the electrocardiograph, heart rate, pulmonary and abdominal arterial pressure, and aortic flow. Three contrast media, ioxitalamate, ioxaglate, and iopamidol (two ionic and one nonionic), were compared, either concentrated (32% iodine) or dilute and isotonic with plasma (ioxaglate 160 mg I/mL and iopamidol 128 mg I/mL). At an injection rate of 5.12 g I/second, iopamidol-128 showed lower electrophysiologic tolerability and caused a higher increase in aortic flow than ioxitalamate 160 or ioxaglate 160. These effects may explain the lower radiographic efficacy observed with iopamidol-128 in previous digital subtraction angiography studies.

Angiography↗
PubMed1988

Gd-DOTA, a potential MRI contrast agent. Current status of physicochemical knowledge.

The complex (Gd-DOTA) meglumine has recently been used as an MRI contrast agent in humans. Due to its particularly interesting physicochemical properties, the risk of in vivo dissociation of the complex is reduced. Indeed, as a result of the macrocyclic nature of the DOTA ligand, Gd-DOTA appears very stable, demonstrating a calculated conditional stability constant of 10(22.19) at pH = 7. Other characteristics making Gd-DOTA a positively attractive compound include slow dissociation kinetics inherent in the rigidity of the macrocycle and marked specific affinity of DOTA for gadolinium in comparison with other endogenous ions. Finally, although the relaxivity R1 of Gd-DOTA at 20 MHz appears similar to that of Gd-DTPA, Gd-DOTA demonstrates higher paramagnetic efficacy at low field strength due to greater symmetry of the complex. Such promising properties open up wide prospects for the use of Gd-DOTA in MRI.

Contrast Media↗
PubMed1988

Experimental study of DOTA-gadolinium. Pharmacokinetics and pharmacologic properties.

Pharmacokinetic and acute-toxicity studies of Gd-DOTA meglumine (Mgl) were evaluated in various animals and compared with those of Gd-DTPA Mgl. The agents were injected intravenously at two dosages: 0.1 or 0.5 mmol/kg. Various organs and tissues were removed at specified times after injection and assayed for gadolinium (Gd) concentration. The two complexes behave in an identical fashion in their short-term biodistribution and excretion. The very rapid distribution in the body (except in the brain) and the high clearance from blood are due to an extravascular distribution. The small distribution volume and the very high hydrophilicity account for its extracellular localization. There is no accumulation within any organ. Rapid disappearance, short half-life, size, and hydrophilicity of these molecules are in agreement with urinary elimination by free glomerular filtration. Whatever the species or the salt used, Gd-DOTA appears safer in its acute toxicity than Gd-DTPA with an 85% higher safety factor. These results can be explained by the greater stability of Gd-DOTA (very slow kinetics of dissociation and greater specificity of DOTA than DTPA for gadolinium), and the lower osmolality of DOTA than DTPA. The pharmacokinetic characteristics and the very low toxicity of Gd-DOTA Mgl may prove its suitability for intravenous or oral administration in humans.

Animals↗
PubMed1987

Incidence of ventricular fibrillation during coronary arteriography in the rabbit. A comparative study of isotonic ioxaglate and iohexol.

The incidence of major ECG changes, particularly ventricular fibrillation, was evaluated in rabbits during prolonged, selective right coronary injection of sodium/meglumine ioxaglate (Hexabrix 160) and iohexol (Omnipaque 140), two isotonic contrast media. The anesthetized animals (n = 12) per test solution) each received 1.5 ml of contrast material, delivered at a rate of 3 ml/minute. Both contrast media caused major ECG changes, which were reversible within seconds after administration. No fibrillation occurred with ioxaglate, but ventricular fibrillation was seen in seven animals given iohexol. There was a significant difference in the incidence of ventricular fibrillation between the contrast media (P less than .01). Both test solutions induced transient, more or less marked bradycardia, but without significant differences. The intracoronary injections produced similar decreases in blood pressure for both contrast agents. Reactive hypertension was observed only in those animals in which an episode of fibrillation occurred with iohexol. The causes underlying these effects are analyzed for both contrast agents.

Animals↗
PubMed1987

Study of isotonic contrast media in intravenous digital subtraction angiography.

Arterial enhancement obtained with isotonic contrast media in intravenous digital subtraction angiography was studied. Ten dogs were injected with ioxaglate, iopamidol, and ioxitalamate at equal iodine concentration and at concentrations corresponding to plasma osmolality. Three variables were studied: osmolality, injection rate, and iodine dose. Provided their iodine concentration is sufficient, isotonic contrast media appear as efficient as the corresponding hypertonic formulation, at equal iodine dose. Moreover, the use of isotonic ioxaglate allows a lower dose of iodine to be administered without significant reduction in peak arterial value.

Animals↗
PubMed1986

Action of gadolinium complexes on different enzyme systems.

Gadolinium complexes have two advantages: their toxicity is very low and the paramagnetic properties are adequate enough to give a useful signal with magnetic resonance imaging (MRI). The effects of several MRI contrast media on the activity of two brain enzymes, glutamate decarboxylase (GAD) and cholineacetyl transferase (ChAT), were investigated. The study was performed on homogenates of rat striatum with variable concentrations of gadolinium sulphate, EDTA, DTPA, DOTA, Gd-EDTA, Gd-DTPA and Gd-DOTA (from 10(-2) mol/l to 10(-9) mol/l. Gadolinium in its ionic form and the chelators of cation agents such as EDTA, DTPA and DOTA inhibit GAD, a calcium dependent enzyme, whereas they have no inhibiting effect on the activity of ChAT, a calcium independent enzyme. Gadolinium complexes inhibit the GAD activity by about 15 per cent whereas they do not modify that of ChAT. The complex form of gadolinium has the advantage of retaining its paramagnetism while drastically lowering its toxicity.

Animals↗