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Biomedical subjects

G Desch

Publications and source records attributed to G Desch.

34 records · Page 2Linked to original sources

[Maternal and fetal levels of local anaesthetics after epidural injection of a triple mixture].

Twenty-four parturients received an epidural injection of a 5.10(-6) adrenaline mixture containing: lidocaine 295 +/- 19 mg, bupivacaine 58 +/- 4 mg and etidocaine 58 +/- 4 mg. The mean serum levels measured in the mother (peripheral vein) and in the fetus (umbilical vein) and in the fetus (umbilical vein) and the fetus/mother ratios were, respectively:--1.05 +/- 0.47 micrograms . ml-1, 0.68 +/- 0.34 micrograms . ml-1 and 0.66 +/- 0.15 for lidocaine; --0.25 +/- 0.10 micrograms . ml-1, 0.14 +/- 0.06 micrograms . ml- and 0.51 +/- 0.16 for bupivacaine; ---0.27 +/- 0.10 micrograms . ml-1, 0.17 +/- 0.10 micrograms . ml-1 and 0.63 +/- 0.23 for etidocaine. From the sum of these concentrations the maternal and fetal serum levels and the fetus/mother ratio could be calculated in lidocaine equivalents. The values obtained were: 3.14 +/- 0.74 . ml-1, 1.90 +/- 0.68 micrograms . ml-1 and 0.60 +/- 0.13 respectively. A comparison of these data with those found in the literature led to the following conclusions: (1) The maternal serum levels of each anaesthetic drug in the mixture are the same as if it had been injected separately; (2) owing to tissue competition, the transplacental passage is increased by majoration of the free form, this being more pronounced with bupivacaine and etidocaine; (3) the circulating drug concentrations evaluated as lidocaine equivalent in the mother and fetus are comparable to those determined at the end of conventional local anaesthetic procedures.

Anesthesia, Epidural↗

Effect of acetate on ketogenesis during hemodialysis.

The concentration of plasma acetate, glucose, and ketone bodies were determined for both venous and arterial blood before and at the end of dialysis with an acetate-containing dialysate. We also determined lactate and pyruvate levels in arterial plasma. The results obtained in the same patients were compared when dialysis were done with or without glucose and discussed in terms of hormonal changes (insulin, glucagon). Arterial plasma acetate (p less than 0.001) and ketone body levels (p less than 0.05) increased significantly during dialysis both with glucose and without glucose (p less than 0.001 in both cases). Higher end-dialysis arterial levels were found for the latter set of glucose-free dialysis (p less than 0.05 and p less than 0.001, respectively, for acetate and ketone bodies), and a correlation was established between end-dialysis arterial concentrations of acetate and ketone bodies. This suggests high consumption of both endogenous and exogenous acetate to feed ketogenesis. This is concurrent with decreased insulin and high glucagon levels. Under these conditions, plasma accumulation of ketone bodies would facilitate an indirect elimination of acetate by the dialyzer (about 10% of the acetate load). Our results suggest that hormone variations during glucose-free dialysis which promote fatty acid oxidation and ketogenesis from acetyl groups hinder acetate-dependent lipogenesis.

3-Hydroxybutyric Acid↗

[Pharmacokinetics of local anesthetics].

This article first looks at the pharmacokinetics of local anesthetic agents injected intravenously, and then looks at the possible practical applications of this technique: the choice of a local anesthetic agent as a function of its toxic side effects, the use of lidocaïne in local and regional intravenous anesthesia, and the treatment of cardiac rhythm disorders. Finally the article envisages the pharmacokinetics of local anesthetic agents used in local-regional anesthesia. This depends on the following factors: the site of injection, the dosage, the speed of injection, the possible addition of adrenalin and the nature of the local anesthetic itself. On the basis of a personal study the authors underline the difficulty of being precise in the pharmacokinetics of local anesthetic agents injected by the peridural route continuously or discontinuously.

Anesthesia, Conduction↗

[Rapid simultaneous assay of the principalamide-type local anesthetics by gas-liquid chromatography].

This method can assay simultaneously, using 300 microliters of plasma, of the three principle local anesthetic agents used by peridural injection for post-operative anesthesia and analgesia: xylocaïne, etidocaïne, bupivacaïne. The assay method consists of three steps: (a) the addition of an internal calibrating agent (mepivacaïne). (b) defecation using trichlorocetic acid. (c) alcalinization of the supernatent (pH 11), extraction with dichloromethane and concentration at room temperature of the organic phase. (d) chromotography using an SE 30 or OV 17 impregnated column. The method is sensitive between 0.37 mumoles per l-1 (0.1 microgram . ml-1) and the coefficient for the mean deviation is 10.9% for concentration between 0.37 mumoles 1-1 and 75 mumole1-1 (0.1 microgram . ml-1 and 20 micrograms . ml-1). The correspondence of the figures recorded in this large concentration range without any change in the technique means that the kinetics of the plasma concentrations before and after peridural injection can be followed. The results obtained by gas liquid chromatography for the assay of lidocaïne were compared in 115 different plasma samples with concentrations obtained by an immuno enzymatic method ("EMIT") fitted to a centrifuge analyser. The correlation coefficient between the two methods was: (r = 0.95 with y = 0.09 x +0.25 microgram . ml-1 implying the absence of any interference and the specificity of the two methods. The columns also separate in 20 minutes the two main metabolites of lidocaïne: monoethylglycinexylidide (M.E.G.X.) and glycinexylidide (G.X.). These results demonstrate that continuous peridural injection of lidocaïne produces a high plasma concentration without any clinical toxic phenomena.

Anesthetics, Local↗

[Decrease in BSP clearance during epidural anesthesia at a constant flow rate. Clinical implications].

The fractional clearance K1 of bromsulphthalein was measured in twelve surgical patients at an interval of a least 48 hours. The first measurement was performed pre-operatively and the second postoperatively 24 hours after the operation, whilst the patients were receiving analgesia by the epidural injection of lignocaine at a constant flow rate. Between the two determinations there was a fall in BSP clearance of 25 +/- 11 p. 100 (range: -8 and -40 p. 100) P less than or equal to 0.0001. The clinical implications are discussed on the basis of concrete examples.

Adult↗

[Comparison of postoperative blood levels of prolactin and somatotropin after two methods of anesthesia].

Prolactin and somatotrophin were measured during the postoperative period in two series of 15 patients after gynaecological surgery. Samples were collected for four days at the same times during the 24 hours period. The anesthetic given in the first group was a neuroleptanalgesia of dextromoramide-droperidol type followed by postoperative analagesia using a noramidopyrine compound. In the second group, epidural anaesthesia was given, followed postoperatively by the injection of lidocain at constant rate interrupted between the final two samples. In the neuroleptanalgesia group, from a basal levels of 11 micrograms.l-1, prolactin rose to 22 micrograms.l-1 on the evening after surgery (p less than 0.001) to subsequently stay on a plateau between 6 and 8 micrograms.l-1 (p less than 0.025 to p less than 0.005). From a basal level of 2.8 micrograms.l-1, somatotrophin rose to 9 micrograms.l-1 (p less than 0.05) then fell progressively from 7.5 to 2 micrograms.l-1 (NS on D1, D2, D3). In the epidural group, from a basal level of 13.5 micrograms.l-1, prolactin rose to 23 micrograms.l-1 on the evening after surgery (NS) to fall sharply on D1 to 5.6 micrograms.l-1 (p less than 0.01) and then follow a plateau on D2 and D3 of the order of 11 to 12 micrograms.l-1 (NS). From a basal level of 1.9 micrograms.l-1, somatotrophin rose to 10 micrograms.l-1 (p less than 0.001) to fall again to 4.5 micrograms.l-1 on D1 (p less than 0.01) and to 2 micrograms.l-1 on D2 and D3 (NS). Comparison of these two groups showed a difference only on D2 with regard to somatotrophin (p less than 0.05) and on D2 and D3 with regard to prolactin (p less than 0.025 and p less than 0.05). These results are discussed. They do not indicate any fundamental difference in the endocrine response to aggression in relation to the two types of anaesthetic studies.

Anesthesia↗

[Postoperative analgesia by constant flow injection of lignocaine in obstetrical and gynecologic surgery].

154 surgical patients were given post-operative analgesia by peridural injection at a constant flow in the post-operative period after obstetric or gynecological surgery. These patients received 536.2 +/- 105.3 mu mol.h-1 (145.2 +/- 28.5 mg.h-1) of lignocaine for 46.97 +/- 15.56 h through a catheter omserted between L1-L2. The drug was given in concentrations which varied between: 27.7 to 18.5 m mol.l-1 (0.75 to 0.50 p. 100) depending on the age; and the volume varied between 17.5 to 30 ml.h-1 depending on the height. Satisfactory analgesia in 87 p. 100 of cases allowed all supplementary analgesia to be stopped. The only significant hemodynamic effect was a slight tachycardia (+ 15 p. 100). Two undesirable side effects were noted: a transitory but well-defined (type 2 or 3) motor paralysis, and an accumulation of plasma lignocaine (40 mu mol.l-1 (1.1 microgram.ml-1) at 48 h).

Analgesia↗

Plasma acetate levels during hemodialysis.

Before dialysis, acetate levels in hemodialyzed patients (0.27--1.1 mmol/1) were more dispersed than in normal subjects (0.20--0.65 mmol/l) and the mean value of plasma acetate was slightly higher (0.52 mmol/l versus 0.31 mmol/l). Though dialysis conditions were almost identical, the acetate kinetics during hemodialysis were very different: in most subjects, plasma acetate concentrations reached a "plateau" (mean value 5.6 mmol/l) whereas in others a continuous rise was observed, suggesting that with patients having chronic renal failure there were important individual or occasional differences in the ability to metabolize acetate. The acetate loads per minute (or mass transfers) were calculated from the blood compartment with plasma values (plasma flow and concentrations), rather than from the dialysate and using the combined calculations (plasma and whole blood values). The results ranged between 2.4 and 4.1 mmol/min. A very important and rapid fall in arterial acetate concentrations occurs in the first 20 min after the end of the dialysis and proves the rapid turnover of the acetate in man.

Acetates↗

[Rapid gas chromatographic method for determination of acetate in human plasma and hemodialysis baths (author's transl)].

A rapid and sensitive method for acetate determination in human plasma and in hemodialysis baths (dialysates) is going to become necessary owing to the extensive using of sodium acetate solution in hemodialysis. The gas chromatographic method reported here allows, in about 35 minutes, the precise and reproducible measurement of acetate concentrations ranging from 0.2 to 20 mmol/1. This method can be used to investigate the kinetics of acetate concentration variations in the blood of patients undergoing hemodialysis with sodium acetate solution and to evaluate the amount of acetate absorbed during this treatment.

Acetates↗

[Biomarkers of tobacco smoke exposure].

Tobacco smoking is a major risk factor for cancer, cardiovascular diseases and respiratory illnesses. Smoking is increasing among children and adolescents with subsequent consequences on the health. Furthermore, maternal tobacco smoking during pregnancy adversely affects prenatal growth. Nicotine, the most important tobacco alkaloid, is responsible for maintaining tobacco addiction. According to a recent Circulaire de la direction générale de la santé, nicotine dependence should be determined through questionnaires and quantitative estimate of nicotine metabolites. Nicotine blood level fluctuates and urinary nicotine excretion is of short duration. Nicotine is intensively metabolized in the liver and oxidized into cotinine. Urinary measurement of cotinine appears to be highly related with the degree of intoxication and to allow the differentiation between non exposed and exposed non-smokers. In order to check the present application of nicotine metabolites measurement, a survey was conducted in 340 smoking cessation units. Forty percent physicians (n = 137) answered the survey. For 17% of them, the quantification of nicotine metabolites is included in their daily practise and for 79%, guidelines about cotinine measurement should be given in France. Sixty-seven biologists answered the survey. Recommendations for immunoassay and HPLC determination of cotinine should be given as reported by 66 and 44% of them respectively. Indeed, urinary cotinine measurement with high performance liquid chromatography is highly sensitive and specific. However, immunoassays are more convenient. These two approaches are presently under investigation in order to provide guidelines for optimal use in various clinical situations. Traditional measures for nicotine dependence are the number of cigarettes smoked per day, nicotine intake expressed as mg per day, Fagerstr m questionnaire, expired air carbon monoxide, thiocyanates and cotinine levels in biological fluids. Urinary cotinine measurement is the most useful for the follow-up of smoking cessation including adjustment of nicotine replacement therapy, especially after a clinical event or for the follow-up of smoking pregnant women. It allows the detection of passive smoke exposure in children who are hospitalized for recurrent respiratory illnesses.

Biomarkers↗

[Biomarkers for toxicity and metabolic abnormalities of the main severe poisonings. Clinical and toxicologic symptoms. Conservative determination].

The members of the joint group "Toxicology and Clinical Biology" of the French Society of Clinical Biology (SFBC), the French Society of Analytical Toxicology (SFTA), and the Society of Clinical Toxicology (STC), suggest guidelines to meet the requirements of clinical biologists who are not specialized in toxicology. Based on good laboratory practice they propose a number of guidelines. Three synthetic tables have been established. They are not only toxicity biomarkers and metabolic disorders associated with the main severe intoxications, but also clinical signs that are observed during these intoxications, finally biological sampling as a precautionary measure. The table also takes into account approximately fifty xenobiotics: main clinical signs emergency, identification or quantification of the suspected product, useful biological markers, therapeutic, quantitations necessary to take into consideration patient care, and poison antidotes, are described. Recommendations regarding medical and forensic techniques are also proposed by the group. It is also necessary to collect and store biological samples when the individual patients are in charge. These samples will be analyzed or not depending on the individual case history.

Biomarkers↗

[Urinary cotinine and nicotine metabolites measurement].

UNLABELLED: According to the recent regulations (Circulaire DGS/DH du 3 avril 2000), tobacco dependence must be determined by the measurement of urine nicotine metabolites. Various assay methods are presently available. They were tested in order to evaluate their analytical performances and to determine how they can be used for the clinical management of smoking cessation. MATERIAL AND METHODS: Urine samples from a single void (n = 97) were obtained from active and abstinent smokers (with or without nicotine substitutive therapy). They were all analyzed by the various methods. Cotinine concentration was measured in six laboratories, using HPLC combined with UV detection according to a standardized procedure (Ann Biol Clin 2002 : 60 : 263-72). Immunoassay methods were also tested and the values obtained from urine samples were compared to urine cotinine measured by HPLC-UV. RESULTS: HPLC-UV: Urinary cotinine varied in a range from undetectable to 4 mg/L. An interlaboratory comparison was performed according to the Valtec procedure (calculation of equation of Deming, chart of differences). There was a good accordance between laboratories. Cotinine concentration was only slightly influenced by fluid intake, as shown by a poorly significant correlation between cotinine and creatinine (r = 0.23, p = 0.05). Homogeneous immunoassays: The two homogeneous immunoassays (Cotinine) from Thermo Electron and Cotinine Enzyme Immunoassay commercialized by Microgenics were highly correlated (r = 0.97). The correlation was not so strong with HPLC-UV (r = 0.86). Firstly, values were found higher with immunoassays because antibodies crossreact with 3-hydroxycotinine. Secondly, the ratio of immunoassays values to HPLC-UV values varied according to urine specimens. Finally, there was a highly significant correlation with urine creatinine (r = 0.40, p = 0.0001), thus indicating the influence of fluid intake. Heterogeneous immunoassay: The kit Metabolites of Nicotine commercialized by DPC France was tested on the analyzer Immulite, using a procedure specifically established for urine. Antibodies revealed a large spectrum of nicotine metabolites. Therefore, the values were much higher than those observed for the same urine samples with homogeneous immunoassays. CONCLUSION: HPLC-UV can be recommended for the measurement of urinary cotinine, as it was shown a good accordance between laboratories. The low detection limit is of interest for the diagnosis of Environmental Tobacco Smoking. Homogeneous immunoassays can be easily used for routine analysis as they can be performed directly on urine specimen. The results must be interpreted according to cut-off values specifically established according to homogeneous or heterogeneous immunoassays. Variability induced by fluid intake must be taken into account. The interest of the heterogeneous immunoassay needs to be confirmed for the diagnosis of Environmental Tobacco Smoking.

Chromatography, High Pressure Liquid↗

[Measurement of urinary free cotinine. Comparison with the level of expired air carbon monoxide].

BACKGROUND AND AIM: Cotinine is a very reliable index for the estimation of active or passive smoking. Sampling from a single urine void is well accepted by smokers who are willing to stop. It is not possible to exclude modification of urine cotinine according to beverage intake. The aim of this study was to determine if urine cotinine concentration must necessarily be adjusted to creatinine or not, by making comparison with expired air carbon monoxide. MATERIAL AND METHODS: Carbon monoxide was measured in 53 smokers coming for the first time in a smoking cessation program. Urine cotinine was measured by HPLC-UV. The cut-off value for abstinence is 8ppm and 0.05 mg/L, repectively. Urine creatinine was determined using the Jaffe reaction. RESULTS: Mean CO level was 18.5 +/- 10.6 ppm and mean urine cotine was 1.45 +/- 0.86 mg/L. Eight smokers had CO 8 ppm. They should be considered as abstinent. However, only one of them had a cotinine under the detection limit. Urine creatinine varied in a large range (0.7 - 35 mmol/L). But, cotinine was only weakly correlated to creatinine (r = 0.279, p = 0.037). There was a highly significant correlation between cotinine and CO (0.649, p = 0.0001). The correlation of cotinine/creatinine versus CO was not significant (r = 0.249, p = 0.072). In order to take into account fluid intake, urine cotinine of each sample was adjusted as if creatinine was equal to the mean (8.3 mmol/L) of the group of subjects. The correlation observed with adjusted or non adjusted cotinine and CO (r = 0.640, p < 0.0001) was the same. CONCLUSION: Urine cotinine from a single void is an accurate index of tobacco smoking at the individual level. There is no need to adjust cotinine concentration, taking into account urine creatinine. Measurement of urine cotinine can be useful to manage smokers who deliberately wish to overcome tobacco dependence, offering the opportunity to provide an adequate level of nicotine substitutive therapy. It is also of peculiar importance to follow-up pregnant women and smokers for whom cessation is required after a clinical event. Finally, absence of cotinine in urine can be used to document abstinence from tobacco products.

Adult↗