[Guidelines relative to the collection and handling management of biological samples]. / Recommandations pour la maîtrise de l'étape de prélèvement des échantillons biologiques.

Guidelines relative to the management of samples collection and handling for common tests are proposed with a list of websites to improve knowledge concerning the practices of biological sampling. Then, methodology is given for the creation of an electronic primary sample collection manual for medical laboratory tests. A list containing the medical laboratory tests for which the information and/or particular documents are needed either for the request or interpretation is presented. Another list for some specific laboratory tests with special individual requirements is proposed. We give also items allowing a standardized description of laboratory tests to help to create a personalized list of the available examinations, facilitating the information of professionals.

[Multisite validation of CDT measurement by the %CDT TIA and the Tina Quant %CDT kits]. / Validation multicentrique du dosage de la CDT par les méthodes %CDT TIA et Tina Quant %CDT.

The measurement of CDT (Carbohydrate Deficient Transferrin) is an essential biological tool in the diagnosis and follow-up of alcohol abuse. It is also employed as a marker of abstinence for the restitution of driving licences. However, the precision of measurement, and the between laboratory homogeneity of the results are still discussed. The ion exchange followed by immunodetermination of CDT is available in two products, the Tina Quant %CDT (Roche, Mannheim, Germany) and the %CDT TIA (Bio-Rad, Hercules, United States). This multicentre study was undertaken: 1) to evaluate the analytical characteristics of these kits and the homogeneity of the results from one laboratory to another, independently of the method used, 2) to validate the differences between the proposed normal values of both kits, 3) to study the possibility of using commercial control sera as external quality control. Four analytical systems were included in the study (Roche Modular/Hitachi 717, Beckman Coulter Immage and LX20, Dade Behring BNII). Determinations were carried out on pools of sera, commercial control sera, kit controls, and 30 serums of patients. These latter were also analyzed in capillary electrophoresis in order to establish correlations between the techniques. The calibrations were stable over one 2 weeks period. The repeatability of measurements spread out from 3,1% to 24,7%, for a mean value lower than 10%. The commercial control sera provided reliable results, with values adapted to a routine quality control use. The results of the Bio-Rad applications were lower by approximately 20% than those of the Roche application, which justifies the difference of the normal values (2,6% versus 3%), and an identical classification of the patients in at least 27 of the 30 samples. We conclude that the analytical quality of the compared techniques, even if it could be improved, is sufficient to guarantee a good reliability of the results. An external quality control could be proposed by using the control sera that we tested.

[Measurement of urinary free cotinine. Comparison with the level of expired air carbon monoxide]. / Dosage de la cotinine urinaire libre. Deuxième partie: comparaison avec le taux de monoxyde de carbone dans l'air expiré.

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.

[Urinary cotinine and nicotine metabolites measurement]. / Dosage urinaire de la cotinine et des métabolites de la nicotine.

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.

[Biomarkers for toxicity and metabolic abnormalities of the main severe poisonings. Clinical and toxicologic symptoms. Conservative determination]. / Biomarqueurs de toxicité et anomalies métaboliques dans les principales intoxications graves. Symptomatologie clinique et toxique. Le prélèvement conservatoire.

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 of tobacco smoke exposure]. / Les marqueurs spécifiques du tabagisme.

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.

[Responsibilities of the emergency service of the federal army in foreign interventions]. / Aufgaben des Sanitätsdienstes der Bundeswehr bei Auslandseinsätzen.

The security environment of our country has undergone a fundamental change since the end of the East-West confrontation. This has led to an extension of the Federal Armed Forces' mission to include, apart from military national defence, participation in multinational and supranational missions abroad. The Medical Service must adapt to this new mission. Emphasis is no longer placed on medicine with limited means, but rather on field medical support, whose procedures and measures guarantee a level of quality in missions abroad which is equal to the standard of medical care in Germany. Surgery in field operations comprises the entire spectrum of surgical medicine and makes it necessary to have field surgeons who have received follow-on training, particularly in traumatology. Preclinical care is conducted in rescue stations and rescue centres which fall under the responsibility of the Services, while immediate clinical care is provided in the hospitals and station hospitals of the central medical service.

Comparative electrophysiologic and hemodynamic effects of several amide local anesthetic drugs in anesthetized dogs.

Large and equipotent doses of several local anesthetics were administered in a cardiac electrophysiologic model on closed-chest dogs. Five groups of pentobarbital-anesthetized dogs were each given intravenously 16 mg/kg lidocaine, 12 mg/kg mepivacaine, 4 mg/kg or 8 mg/kg etidocaine, and 4 mg/kg bupivacaine. Lidocaine induced bradycardia, slowing of atrioventricular node conduction (AH), and marked hemodynamic depression, represented by a decrease in mean aortic pressure (MAoP), in the peak of first derivative of left ventricular pressure (LVdP/dt(max)) and by an increase in left ventricular end-diastolic pressure (LVEDP). Atrial pacing at pacing cycle length (PCL) of 298 ms did not enhance the alteration of variables of ventricular conduction (His ventricle [HV] interval and QRS duration). Mepivacaine induced slight alteration of electrophysiologic variables. Atrial pacing at PCL of 312 ms did not enhance the alteration of HV and QRS duration. Mepivacaine induced transient hemodynamic depression. Etidocaine (4 mg/kg) induced electrophysiologic and hemodynamic alterations similar to mepivacaine but artrial pacing at PCL of 330 ms enhanced HV lengthening and QRS widening (P < 0.05). Etidocaine (8 mg/kg) induced marked impairment of PR, HV, QRS, and QT, and dramatic hemodynamic depression represented by a decrease in MAoP from 123.5 +/- 16.2 at baseline to 36.5 +/- 8.3 mm Hg at 1 min (P < 0.001) and of LVdP/dtmax) from 1446 +/- 379 to 333 +/- 93 mm Hg/s (P < 0.001). Bupivacaine induced dramatic impairment of electrophysiologic variables. Bupivacaine also decreased LVDP/dtmax (from 1333 +/- 347 to 617 +/- 299,P < 0.001) and increased LVEDP. We conclude that mepivacaine induced moderate cardiotoxicity. In contrast, lidocaine induced dramatic hemodynamic depression while etidocaine and bupivacaine markedly impaired both electrophysiologic and hemodynamic variables. This double impairment could explain the great difficulty in resuscitating patients who have had cardiotoxic accidents induced by etidocaine or bupivacaine.

Spinal anaesthesia in newborns: total and free bupivacaine plasma concentration.

This study was designed to measure total and free bupivacaine (B) after spinal anaesthesia in newborns and to evaluate a possible influence of adrenaline on B absorption. Twenty-two newborns were randomly allocated to receive either plain B (group 1) or adrenaline added to B (group 2) for spinal anaesthesia. A single blood sample was collected ten min after spinal injection. Total B concentration was found 0.31 +/- 0.17 microgram ml-1 in group 1 and 0.25 +/- 0.09 microgram ml-1 in group 2. Bound B concentration was 0.27 +/- 0.17 microgram ml-1 in group 1 and 0.22 +/- 0.09 microgram ml-1 in group 2. No difference was found between the two groups for these parameters. Albumin but not alpha 1-acid-glyco-protein correlated to age and weight, bound B correlated to alpha 1-acid-glyco-protein but not to albumin. Despite the low plasma concentration of binding proteins in newborns, spinal anaesthesia with B does not result in a high level of free drug. Adrenaline does not have any pharmacological advantage in these patients.

Receptor mechanisms for clonidine reversal of bupivacaine-induced impairment of ventricular conduction in pentobarbital-anesthetized dogs.

Possible mechanisms of the ability of clonidine to correct bupivacaine-induced ventricular electrophysiologic impairment were evaluated in an electrophysiologic model on closed-chest dogs. Nine groups (n = 6) of pentobarbital-anesthetized dogs were given atropine, 0.2 mg/kg intravenously (i.v.), and bupivacaine, 4 mg/kg i.v., over a 10-s period. Group 1 was then given only saline solution. Group 2 was given clonidine, 0.01 mg/kg i.v., over a 1-min period. Group 3 was given clonidine followed by i.v. administration of yohimbine, 1 mg/kg, an alpha 2-antagonist. Group 4 was given carbachol, 1 mg/kg i.v., a long-lasting cholinergic agonist, over a 1-min period. Group 5 was given electrical stimulation of the left vagus nerve. Group 6 was given physostigmine, 0.1 mg/kg i.v., known to inhibit cholinesterase degradation, 5 min before bupivacaine administration, and Group 7 received a combination of physostigmine pretreatment and electrical vagal stimulation. Group 8 was given physostigmine, 0.1 mg/kg i.v., and pancuronium bromide, 1 mg/kg i.v., known to inhibit nicotinic receptors, 5 min before bupivacaine administration. Then electrical stimulation of the left vagus nerve was performed. Group 9 was given nicotine, 0.1 mg/kg i.v., 1 min after bupivacaine injection over 1 min. Bupivacaine induced bradycardia, markedly increased the His-Purkinje conduction time (HV interval) and QRS duration. Bupivacaine decreased the peak of first derivative of left ventricle pressure (LVdP/dtmax) and increased left ventricular end-diastolic pressure (LVEDP). Clonidine improved QRS duration and HV interval. Yohimbine did not modify the effects of clonidine. QRS duration and HV interval were significantly improved in Groups 4-7. In Group 8, pancuronium pretreatment inhibited the beneficial effects of the combination of physostigmine pretreatment and electrical vagal stimulation. In contrast, in Group 9, like clonidine, nicotine improved QRS duration and HV interval. Three other groups of anesthetized dogs (n = 6) were then studied. All dogs were given hexamethonium, 10 mg/kg i.v. Then, Group 10 was given only saline solution; Group 11 was given bupivacaine, 4 mg/kg, and Group 12 was given bupivacaine and nicotine as in Group 9. In Group 11, bupivacaine induced its usual alterations. In contrast, nicotine did not modify the cardiotoxic profile of bupivacaine after hexamethonium pretreatment. We conclude that the beneficial effect of clonidine on the variables of ventricular conduction altered by bupivacaine 1) is not mediated by central alpha 2-activation, 2) is mediated by the activation of parasympathetic pathways, and 3) is indirect and not mediated by acetylcholine release but is mediated by the activation of parasympathetic ganglionic nicotinic receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Mechanisms of the putative cardioprotective effect of hexamethonium in anesthetized dogs given a large dose of bupivacaine.

BACKGROUND: Some reports suggest that activation of the autonomic nervous system by bupivacaine could participate in its cardiotoxicity. This is based in part on the fact that hexamethonium suppresses cardiac disturbances in anesthetized rabbits given small intracerebroventricular doses of bupivacaine. The aims of the current study were to determine, in anesthetized dogs, (1) whether the activation of the autonomic nervous system is deleterious after a large intravenous dose of bupivacaine and (2) whether the parasympathetic or sympathetic system is implicated in the bupivacaine-induced deleterious activation of the autonomic nervous system. METHODS: We used an electrophysiologic model in closed-chest dogs anesthetized with sodium pentobarbital. In group 1 (n = 6), dogs were given 4 mg/kg intravenous bupivacaine over 10 s. In group 2 (n = 6), dogs were given the same dose of bupivacaine 5 min after having received 0.2 mg/kg intravenous atropine sulfate. In group 3 (n = 9), dogs were pretreated with 10 mg/kg intravenous hexamethonium and then given bupivacaine 4 mg/kg. In addition, in group 3, the right atrium was paced at a basic cycle length of 400 ms to obtain a heart rate similar to that of group 1. RESULTS: Bupivacaine in group 1 induced significant bradycardia; lengthening of PR, atria-His, His-ventricle, and QTc intervals; and QRS widening. The first derivative of left ventricular pressure was significantly decreased, whereas left ventricular end-diastolic pressure was increased. Atropine pretreatment did not modify cardiac disturbances induced by bupivacaine. Hexamethonium pretreatment induced significantly less QRS widening and QTc lengthening than was seen in group 1 but worsened the bupivacaine effects on bradycardia, atria-His and PR intervals, mean aortic pressure, and first derivative of left ventricular pressure. Moreover, atrial pacing in group 3 induced alterations of QRS similar to those in group 1. CONCLUSIONS: Considering that marked slowing of ventricular conduction velocity (i.e., QRS widening) is known to facilitate reentrant ventricular arrhythmias, we conclude that (1) the activation of the autonomic nervous system by bupivacaine is not as deleterious as previously suggested; (2) the parasympathetic system is not markedly implicated in the worsening of direct bupivacaine cardiotoxicity; and (3) the sympathetic nervous system acts only by inducing a less marked bradycardia, which slows ventricular conduction velocity in a use-dependent manner, facilitating reentrant arrhythmias.

Lemakalim, a potassium channel agonist, reverses electrophysiological impairments induced by a large dose of bupivacaine in anaesthetized dogs.

We have examined the ability of lemakalim to correct bupivacaine-induced cardiac electrophysiological impairment in an experimental electrophysiological model in closed-chest dogs. Two groups (n = 6) of pentobarbitone-anaesthetized dogs were given atropine 0.2 mg kg-1 i.v., and bupivacine 4 mg kg-1 i.v. over 10 s. Group 2 received also lemakalim 0.03 mg kg-1 i.v. Bupivacaine induced bradycardia, prolonged PR and His-ventricle (HV) intervals, QRS duration, QTc and JTc intervals, decreased left ventricular (LV) dP/dt max and increased LV end-diastolic pressure. Lemakalim reversed bupivacaine-induced PR, HV, QRS, QTc and JTc prolongation, and did not worsen bupivacaine-induced bradycardia and haemodynamic depression. We conclude that lemakalim can antagonize the main deleterious electrophysiological effects induced by a large dose of bupivacaine in anaesthetized dogs.

Reversal of electrophysiologic and hemodynamic effects induced by high dose of bupivacaine by the combination of clonidine and dobutamine in anesthetized dogs.

The ability of clonidine and dobutamine to correct bupivacaine-induced cardiac electrophysiologic and hemodynamic impairment was evaluated in an experimental electrophysiologic model on closed-chest dogs. Five groups (n = 6) of pentobarbital-anesthetized dogs were given atropine (0.2 mg/kg IV). Group 1 was given a saline solution; all other dogs were given bupivacaine (4 mg/kg IV) over a 10-s period. Group 2 was given only bupivacaine. Group 3 was given clonidine (0.01 mg/kg IV) over a 1-min period. Group 4 was given a dobutamine infusion at 5 micrograms.kg-1.min-1. Group 5 was given the combination of clonidine and dobutamine. Bupivacaine induced bradycardia, prolonged atrioventricular conduction time (PR interval), atrioventricular node conduction time (AH interval), His-Purkinje conduction time (HV interval), and QRS duration. Bupivacaine decreased left ventricular (LV) dP/dt max and increased LV end-diastolic pressure (LVEDP). Clonidine improved QRS duration and HV interval but enhanced AH interval, bradycardia, and hemodynamic depression induced by bupivacaine. Dobutamine infusion improved LV dP/dt max but did not modify bupivacaine-induced ventricular electrophysiologic impairment. The combination of clonidine and dobutamine corrected not only the electrophysiologic impairment induced by bupivacaine but also the hemodynamic depression. As the HV interval and the QRS duration could be correlated with ventricular conduction velocities, we conclude that (a) clonidine reversed the slowing of ventricular conduction velocities induced by bupivacaine, and (b) the combination of clonidine and dobutamine was able to correct the cardiac disturbances induced by bupivacaine in anesthetized dogs.

[Do beta adrenergic receptor blockaders increase bupivacaine cardiotoxicity?]. / Les bêta-bloquants aggravent-ils la cardiotoxicité de la bupivacaïne?

Bupivacaine is known to impair the electrophysiology of the heart as well as haemodynamic parameters. Administration of calcium channel blockers prior to bupivacaine enhances its cardiotoxicity. This study assessed the effects of bupivacaine at toxic dose in dogs with previous beta-adrenergic receptor blockade. It included 12 dogs anaesthetized with thiopentone, allocated in a control group (n = 6) receiving a bolus of bupivacaine (4 mg.kg-1) and a study group (n = 6) treated with the sequence propranolol (0.2 mg.kg-1) and bupivacaine (4 mg.kg-1), 15 min later. Infranodal conduction (HV conduction times and QRS durations) was worsened in both groups. Previous propranolol administration had no potentiating effects on these parameters. Conversely the latter was responsible of a greater decrease in heart rate, and increase in atrio-ventricular conduction time (77.9% vs 18.7%, p less than 0.05), as well as a more severe hypotension. Moreover, 3 out of the 6 animals in the study group suffered a cardiac arrest between the 5th and the 10th min. It is concluded that in anaesthetized dogs the cardiac and circulatory effects of a toxic dose of bupivacaine are increased in case of preexisting blockade of beta adrenergic receptors.

[C-reactive protein in inflammatory articular diseases: comparison of concentrations in blood and synovial fluid]. / La proteine C-reactive dans les affections inflammatoires articulaires: comparison des dosages sanguin et synovial.

We evaluated the diagnostic value of measuring C-Reactive Protein (CRP) in blood and in synovial fluid for the detection of inflammatory articular diseases in 154 patients. High concentrations of CRP in blood were found in microcrystalin arthritis, polymyalgia rheumatica and Horton's disease. Our results show a good correlation between CRP and erythrocyte sedimentation rate for ankylosing spondylitis (p less than 0.01), systemic lupus erythematosus (p less than 0.01), rheumatoid arthritis (p less than 0.05), polymyalgia rheumatica and Horton's disease (p less than 0.05). The CRP measurement in blood did not separate seropositive versus seronegative rheumatoid arthritis, systemic lupus erythematosus versus rheumatoid arthritis and treated versus non-treated rheumatoid arthritis. There was a good correlation between CRP concentration in blood and in synovial fluid but the concentration was lower in synovial fluid than in blood (p less than 0.01). Then, the CRP measurement in synovial fluid does not have a higher diagnostic value than in blood.

Fibronectin is unsuitable as a tumor marker in pleural effusions.

We studied 75 patients with nonmalignant pleural effusions (50 with pneumopathy, 16 with pulmonary tuberculosis, and nine with congestive heart failure) and 33 patients with malignant pleural effusions. We selected 105 mg/L as the most suitable cutoff concentration of fibronectin for distinguishing between the two groups. We found high concentrations of fibronectin in 21 of the 33 patients with malignant pleural fluid but also in 37 of the 75 patients with nonmalignant pleural fluid. Evidently, measuring fibronectin in pleural fluid will not help in differentiating nonmalignant from malignant pleural fluids (diagnostic accuracy: 55%).

Epidural analgesia with a bupivacaine-fentanyl mixture in obstetrics: comparison of repeated injections and continuous infusion.

We compared the efficacy and side-effects of continuous infusion versus repeated injections of epidural bupivacaine-fentanyl during labour. Forty-four parturients were randomly distributed into two groups balanced for population size, morphology and parity. Analgesia was begun at the same stage of labour with a mixture of 20 ml 0.25 per cent plain bupivacaine and 2 ml (100 micrograms) fentanyl. In Group I the initial dose ranged from 8-12 ml as a function of height; an injection of the same dose was repeated immediately upon recurrence of pain. In Group II, after an initial dose of 5-7 ml, a continuous infusion of 3 ml.h-1 was begun, and continued until full dilatation. Analgesia was rated using a pain scale; effects on maternal blood pressure, respiratory rate and neonatal status were noted. Bupivacaine and fentanyl assays were carried out on maternal venous blood in 30 parturients during the course of labour. There was a longer latency to onset of analgesia in Group II (approximately five minutes), followed by a more constant degree of analgesia. This better analgesia cannot be accounted for by a difference in dosage; doses were significantly lower in Group II, despite the fact that labour was of the same duration. The course of labour, and maternal and neonatal status were comparable in the two groups. Assays showed no difference in bupivacaine blood concentrations between the two groups nor signs of drug accumulation. The constant infusion technique is advantageous since it provides a more regular degree of analgesia with lower doses than those required for patients having repeated injections.