Calcineurin Inhibitor Determination in Whole Blood With the RXL Dimension Analyzer: A Useful Tool for Immunosuppressive Drug Monitoring.

Routine monitoring of cyclosporine and tacrolimus levels is necessary to minimize adverse side effects and to ensure effective immunosuppression. The RXL Dimension apparatus conceived for ACMIA technologies is proposed to determine C0 and C2 cyclosporine levels and also tacrolimus levels in whole blood without any dilution or pretreatment using specific calibrators and Flex reagent cartridges (reagent stability: 72 hours for Neoral C0 and C2; 48 hours for tacrolimus). The assay ranges were between 25 to 500 ng/mL for C0; 350 to 2000 ng/mL for C2; and 1.2 to 30 ng/mL for tacrolimus. Within-run and between-day imprecision were <10% for cyclosporine. The coefficient of linearity was r(2) = .998 for C0, C2, and tacrolimus. Moreover, for cyclosporine and tacrolimus assays, the time for the first result was 20 minutes. Cyclosporine (C0, n = 152; C2, n = 54) and tacrolimus (n = 70) ACMIA assays were compared with enzyme-multiplied immunoassay technique (EMIT) cyclosporine and tacrolimus assays (V-Twin, Siemens ex-Dade Behring Laboratories) among 276 transplant patients: 119 kidney, 67 liver, 28 heart, and 62 bone marrow transplantations. Values obtained with the ACMIA assay were highly correlated with the EMIT assay for CsA C0 levels (ACMIA = 1.04 EMIT - 9.32; r(2) = .97); CsA C2 levels (ACMIA = 1.15 EMIT - 53.7; r(2) = .94); and tacrolimus levels (ACMIA = 0.93 EMIT - 0.16; r(2) = .93). In conclusion, the RXL Dimension analyzer is a useful tool for routine monitoring with a single method for C0 and C2 cyclosporine and tacrolimus level determinations in whole blood without any dilution or preanalytic treatment.

Evaluation of a capillary zone electrophoresis system versus a conventional agarose gel system for routine serum protein separation and monoclonal component typing.

Capillary zone electrophoresis of serum proteins is increasingly gaining impact in clinical laboratories. During 2003, we compared the fully automated capillary electrophoresis (CE) system from Beckman (Paragon CZE 2000) with the method agarose gel electrophoresis Sebia (Hydrasis-Hyris, AGE). This new study focused on the evaluation of analytical performance and a comparison including 115 fresh routine samples (group A) and a series of 97 frozen pathologic sera with suspicion of monoclonal protein (group B). Coefficients of variation (CVs %) for the five classical protein fractions have been reported to be consistenly < 9% in within-run and < 10% in between-run imprecision studies with the Paragon 2000 system. The results of the comparison study (group A) demonstrated a good correlation between the CE system and AGE, except for beta-globulin (r = 0.65). Among the 97 pathologic serum samples (group B), there were 90 in which we detected a monoclonal protein by immunofixation (IF) (immunosubtraction (IS) was not used). AGE and Paragon 2000 failed to detect 7 and 12 monoclonal proteins, respectively, leading to a concordance to 92% for AGE and 87% for Paragon 2000 for identifying electrophoretic abnormalities in this group. Beta-globulin abnormalities and M paraprotein were well detected with Paragon 2000. Only 81% (21 vs 26) of the gammopathies were immunotyped with IS by two readers blinded to the IF immunotype. The Paragon 2000 is a reliable alternative to conventional agarose gel electrophoresis combining the advantages of full automation (rapidity, ease of use and cost) with high analytical performance. Qualified interpretation of results requires an adaptation period which could further improve concordance between the methods. Recently, this CE system has been improved by the manufacturer (Beckman) concerning the migration buffer and detection of beta-globulin abnormalities.

Evaluation of an immunoassay (Abbott-IMX Analyzer) allowing routine determination of sirolimus: comparison with LC-MS method.

BACKGROUND: The use of the immunosuppressive agent sirolimus is increasing in renal transplantation but its monitoring often requires high-performance liquid chromatography (HPLC) with ultra-violet (UV) or tandem mass spectrometric (MS-MS) detection. The aim of this study was to compare a new microparticle enzyme immunoassay (MEIA, Microparticle Enzyme Immunoassay) on IMx Abbott Analyser with a liquid chromatography-mass spectometry (LC-MS) method. METHOD: The accuracy of immunoassay analytical performance including within run and between run imprecision and linearity was tested. For comparison studies, sirolimus level was then determined with the two methods on 98 samples from 52 transplant patients. RESULTS: Total intra-assay and inter-assay variation coefficients were below 10% at the three levels tested, and the coefficient of linearity was r = 0.99. The values obtained were highly correlated with the LC-MS method (MEIA = 1.02LC-MS + 0.91; r(2) = 0.87). As a result, the immunoassay showed good performance, and clinical sample measurements were not affected by the method. The MEIA may be a useful alternative for routine monitoring of sirolimus.

Preliminary evaluation of a new chemiluminescence assay (Liaison Cyclosporine; DiaSorin Laboratories) allowing both C0 and C2 cyclosporine levels determination: comparison with RIA method.

Cyclosporine (CsA) monitoring is generally assessed by trough concentration determinations (C0). Recently, the 2-hour postdose CsA level (C2) has been proposed to be a better measurement to predict graft outcome and prevent toxicity. However, using the available methods, C2 determinations require external dilution, which impairs the precision and practicability of the assay. This study assessed the performance characteristics of a new competitive chemiluminescence immunoassay (CLIA, DiaSorin Laboratories, Anthony, France) for the determination of both C0 and C2 CsA concentrations in whole blood on a Liaison analyzer. The results were compared with the RIA method (DiaSorin) used in our laboratory as a reference technique. Analytical performances showed that the total intra-assay variation coefficients (CVs) on the CLIA Liaison ranged from 7.6% to 11.3%, while the between-day imprecision was 11% (15.2%, 11.5%, and 6.5%). The linearity of the method was estimated over the range of 30 to 2400 ng/mL as a correlation coefficient of r = .997. Recoveries, which were checked by adding pure CsA to CsA-free blood, showed a mean value of 86%. A total of 236 whole-blood samples (31% women, 69% men of mean age 45 +/- 17 years) were subjected to a comparative study of CLIA-CsA versus RIA (radioimmunoassay) values, yielding a correlation coefficient >0.90 (CLIA = 0.825RIA+21.611; r(2) > .90). In conclusion, the CLIA Liaison CsA kit represents an alternative to the radioisotopic method, which allows both C0 and C2 determinations without any preanalytical step. The chemiluminescence method demonstrated good analytical performance and practicability in routine use.

The V-twin system (Dade Behring Laboratories): a useful tool for immunosuppressive drug monitoring.

The predose trough cyclosporine (CsA) level (C0) was widely used to assess the possibility of drug nephrotoxicity. Owing to its potential limitation as an indicator of total drug exposure, 2-hour postdose (C2) monitoring has been considered to be a more accurate marker. The V-Twin analyzer (Vital SC, Netherlands) conceived for EMIT technologies (Dade Behring Laboratories) is proposed herein to determine CsA levels using a specific calibrator without any dilution, as well as tacrolimus (FK) and mycophenolate mofetil (MMF) levels. Both CsA (C0: n = 133 and C2: n = 55) and FK (n = 121) EMIT assays were compared to the RIA CsA assay (DiaSorin Laboratory) and to the MEIA tacrolimus assay (Abbott Laboratory), respectively. In addition, the feasibility of MMF EMIT assay was evaluated. Overall, 309 transplant patients were included in this study. For all parameters tested, total imprecision studies were lower than 10%, and the coefficient of linearity was r(2) > .99. For the CsA kit, the range of linearity was between 25 and 500 ng/mL for the C0 and 400 and 2000 ng/mL for the C2 assay. The values obtained were highly correlated with the RIA for the C0 levels (EMIT = 0.9 RIA+3.66; r = .97) and for the C2 levels (EMIT = 0.89 RIA-14.2; r = .956). Similar results were obtained with the EK EMIT kit, with a linearity range between 3 and 30 ng/mL, and a high concordance with the MEIA test (EMIT = 0.98 RIA+1.09; r = .96). Preliminary MMF results in 59 sera, containing from 0.1 to 30 microg/mL, showed that this examination could be included as a routine. The V-twin system is a useful tool for routine monitoring with a single method for C0 and C2 cyclosporine, tacrolimus, and mycophenolate levels.

Metabolism of cyclosporine after orthotopic liver transplantation.

The aim of this work was to determine whether the extensive metabolism of cyclosporine, acquired in a donor by treatment with an inducer of cytochrome P450 3A (P450 3A) (cyclosporine oxidase), was transmissible to the recipient by orthotopic liver transplantation. For this purpose, male Wistar rats were divided into five groups including: control animals (group C), animals treated with dexamethasone (an inducer of P450 3A, 50 or 300 mg/kg/day, for 4 days, group D), animals transplanted with the livers of control rats (group G) or with the livers of dexamethasone-induced rats (group GD), and animals treated with beta-naphthoflavone (an inducer of P450 1A, group B). All animals received a single i.v. dose of 10 mg/kg cyclosporine 24 hr after either the last dose of inducer or the transplantation. For each group of animals, the area under the curve (AUC) of cyclosporine was calculated from the curves of blood cyclosporine levels (by radioimmunoassay) against time; liver microsomes were assayed for cyclosporine oxidase activity by HPLC, erythromycin demethylase and P450 3A level by western blot with specific anti-P450 3A antibodies. The decrease in the AUC in groups D and GD with respect to C and G was correlated with increased level of P450 3A (4-5-fold with respect to control) as well as of microsomal cyclosporine oxidase. In addition, cyclosporine oxidase activity of liver microsomes was specifically inhibited by anti-P450 3A antibodies and troleandomycin. The animals in group B did not exhibit increased metabolism of cyclosporine either in vivo or in vitro. We conclude that: (1) cyclosporine is predominantly oxidized in the rat liver by a form of P450 from the 3A subfamily; (2) the extensive metabolism of cyclosporine acquired by donor rats after treatment with dexamethasone is transmissible to the recipients through orthotopic liver transplantation.

Determination of beta2-microglobulin in biological samples using an immunoenzymometric assay (chemiluminescence detection) or an immunoturbidimetric assay: comparison with a radioimmunoassay.

Monitoring beta2-microglobulin (beta2M) in biological fluids has gained considerable interest in pathologies such as haematologic malignancies, renal diseases, and chronic inflammatory diseases. Due to limitations of the RIA in the routine laboratory, we measure beta2M with non-isotopic methods. 189 patients suffering from myeloma (n=66), end stage renal failure (n=54) or inflammation (n=69) were included in this study. beta2M was determined in serum, urine and dialysate using an immunoenzymometric assay with chemiluminescence detection [Immulite Diagnostic Products Corporation (DPC), La Garenne Colombes, France] and an immunoturbidimetric assay (Olympus, Rungis, France). The data were compared with a radioimmunoassay (Immunotech, Marseille, France) taken as a reference. Using serum samples, the immunoenzymometric assay with chemiluminescence detection and the immunoturbidimetric assay have reliable analytical performances. Values obtained with serum samples are highly correlated with the radioimmunoassay (DPC/RIA r2=0.84; Olympus/RIA r2=0.94) whatever the type of pathology; however an over-estimation which could be related to cross reactivity with beta2M fragments was observed with the RIA method as suggested by crossover calibration and recovery studies. Values obtained with urinary samples (n=96) are closely related to those obtained with the RIA (DPC/RIA r2 = 0.98; Olympus/RIA: r2=0.99). Despite the low levels observed in dialysate (n=57) good correlations were observed between Olympus vs DPC (r2=0.85). By contrast, the two non-isotope methods are poorly related with the RIA method (DPC vs RIA r2=0.47 and Olympus vs RIA r2=0.54). In conclusion, the immunoenzymometric assay with chemiluminescence detection or the immunoturbidimetric assay could be used in the routine laboratory in order to determine beta2M in plasma, urine and dialysate.

[Evaluation of the size of thrombolysed myocardial infarction by serum myosin determination]. / Evaluation de la taille de l'infarctus du myocarde thrombolysé par le dosage de la myosine sérique.

The prognosis of myocardial infarction is very dependent on the size of the infarct. The measurement of the infarct size after thrombolysis remains difficult despite the large number of methods available, all of which have drawbacks. This parameter is however essential to assess prognosis and the efficacy of thrombolytic therapy. Serum beta heavy chain myosin determination is a recently introduced method of evaluating infarct size; there are relatively few published studies, especially concerning post-thrombolytic patients. A prospective study was undertaken in 40 patients (37 men and 3 women: average age 55.6 years) with a primary myocardial infarction treated by thrombolysis. Myosin levels (peak and area under curve of 5 samples in 10 days) were compared with other methods of assessing infarct size: electrocardiogram (number of leads with Q waves, ST segment analysis), cardiac enzymes (peak and release integrals of CK abd LDH), contrast ventriculography (segmental asynergy score, ejection fraction), coronary angiography and resting MIBI myocardial scintigraphy. The peak and integral of myosin release correlated well with the other methods (p < 0.01): a correlation was particularly apparent between the integral of myosin release and MIBI scintigraphy scores (r = 0.77, p < 0.001). Complex myosin release kinetics were observed significantly more often in patients with large infarcts (p < 0.01) or in those with occlusion of the artery responsible for infarction at coronary angiography on the 6th day (p = 0.001). In conclusion, with 5 blood samples over a 10 day period, it is possible to estimate the infarct size after thrombolysis in everyday cardiological practice: this method could help identify high risk subjects (complex kinetics of myosin release and high peak myosin levels) and also could be used to assess efficacy of thrombolytic therapy in large scale trials.

[Prolactin secretion during sleep at puberty. Preliminary results (author's transl)]. / La sécrétion de prolactine pendant le sommeil en période péripubertaire. Résultats préliminaires.

Plasma prolactin was measured in six normal boys, during night sleep, with simultaneous recording of EEG for determination of the various stages of sleep. Peaks of prolactin appear clearly during cycles of rapid sleep: in prepuberty, the average of night peaks of prolactin is higher than that in post-puberty subjects. These results suggest indirectly, a participation of prolactin in prepuberty adrenal maturation.

[Nycterohemeral variations of growth hormone and prolactin in 6 Parkinson's sufferers treated with bromocriptine (author's transl)]. / Variations nycthémérales de la somathormone et de la prolactine chez 6 parkinsoniens traités par bromocriptine.

Secretions of GH and of PRL studied over a period of 24 hours in 6 untreated Parkinson's patients showed slight changes. The normal secretion of PRL in the female shows no nocturnal increase in the male. The secretion of GH linked to sleep is identified in the male and not in the female. These variations related to sex are interpreted as an increase in those normally found in the adult and facilitated by age. Bromocriptine given continuously at a dose of 10 to 20 mg/day for periods of 20 days to 6 months, results in suppression or a marked decrease in the 24-hour secretion of PRL. It has virtually no effect upon the secretion of GH. These results show that the dopaminergic regulation of PRL is preserved in Parkinson's disease.

[Decrease in BSP clearance during epidural anesthesia at a constant flow rate. Clinical implications]. / Diminution des clairances de la B.S.P. sous analgésie péridurale a débit constant. Ses implications cliniques.

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.

[Comparison of postoperative blood levels of prolactin and somatotropin after two methods of anesthesia]. / Comparaison des taux sanguins de prolactin et de somatotrophine en post-opératoire après deux modes d'anesthésie.

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.

Testosterone secretion is severely impaired after hepatectomy in rat, dog and man.

In 90%-hepatectomized rats, the plasma testosterone level (0.34 +/- 0.07 ng.ml, mean +/- SEM) is significantly lower (P less than 0.001) than in sham operated male rats (1.7 +/- 0.26 ng.ml, mean +/- SEM). In dogs, after 90% hepatectomy, the mean plasma testosterone concentration fell to 1/10 of the plasma testosterone level measured in sham operated animals either 24 or 72 h after surgery. In hepatectomized men, plasma testosterone is markedly decreased in contrast to what is observed after duodeno-pancreatectomy performed under the same conditions of anesthesia. These results suggest that 90% hepatectomy severely alters the Leydig cell function.

[Secretions of GH, FSH and LH during sleep of the normal child and the child with retarded growth]. / Sécrétions de GH, FSH et LH au cours du sommeil chez l'enfant normal et avec retard staturo-pondéral

In normal children the major GH release begins during NREM sleep of first cycle. At puberty secretion of gonadotropins is enhanced and secretion of LH occurs with the same periodicity as the sleep cycles. Two groups of dwarfish are seen: the first lacks both GH secretion during sleep and the increase of gonadotropins at puberty. The second group exhibits GH, LH and FSH secretion patterns similar to normal children. Study of secretion patterns of GH, FSH and LH during sleep in children can document the degree of maturation of the hypothalamic pituitary hormonal system.

Increase in sleep related GH and Prl secretion after chronic arginine aspartate administration in man.

Arginine aspartate was administered orally (250 mg/dg/day) for one week to 5 healthy male human volunteers aged 20-35. After this period, the 24 h patterns of growth hormone (GH) and prolactin (Prl) secretion were determined by radioimmunoassay on blood samples withdrawn every 20 min and correlated with the polygraphic recordings of electroencephalogram, electromyogram and electrooculogram. the results were compared to data obtained in identical conditions with the same subjects but after a week of placebo administration. In all 5 subjects the slow wave sleep related GH peak was about 60% higher after a week of arginine aspartate administration than in the control period, with individual changes of +24, +25, +42, +47 and +162%. The nocturnal mean plasma Prl of each subject was higher after arginine aspartate than before. The nocturnal rise of plasma Prl increased from a mean value of +21.5% during the placebo period to +95% at the end of the arginine aspartate treatment. These hormonal modifications were not accompanied by any detectable alteration of sleep organization and specially of the slow wave sleep pattern, suggesting a direct neuroendocrine action of the drug.

Circadian patterns of growth hormone and cortisol secretions in narcoleptic patients.

Narcolepsy, a disorder which is clinically characterized by recurring episodes of sleep during the day, frequently associated with nocturnal disrupted sleep and polygraphically by sleep onset REM periods, has been studied in regard to the relationships between GH, cortisol secretion and sleep. Ten narcoleptics were polygraphically recorded during 24 h after one night's adaptation. Blood samples were taken every 20 min for GH and cortisol immuno-assays. Three narcoleptics were recorded twice 2 months later and 2 normal subjects served as controls. The following results were obtained: GH secretory pattern was different in narcoleptics and controls; two groups were identified: the first one showed a very low basal GH secretion with rare and small secretory peaks not clearly linked with sleep. One subject of this group recorded twice showed a similar pattern. The second group exhibited a higher basal secretion with many peaks without any well-defined relationship to sleep stages. The pattern was again consistent in two recordings of 2 subjects in this group. Furthermore GH secretion rose significantly (p less than 0.01) between 2100 and 0000 with no apparent relationship to sleep stages. The cortisol secretory pattern showed a significant rise (p less than 0.01) between 0400 and 1000 and was not different in narcoleptics and controls. In narcolepsy the monophasic sleep-wakefulness cycle is disrupted. The GH secretion pattern is modified whereas the circadian pattern of cortisol secretion is normal and independent of the sleep-wakefulness cycle of the narcoleptic patient.

[Cyclosporin A metabolism and induction of cytochrome P-450 in orthoptic hepatic transplantation in rats]. / Métabolisme de la ciclosporine A, et induction du cytochrome P450 dans la transplantation hépatique orthotopique chez le rat.

The aim of our study were 1) to establish that cyclosporin (CsA) metabolism was correlated with the rate of cytochrome P4503A (cyt.) in Wistar rats induced with dexamethasone (Dex.), 2) to demonstrate that the induction of cyt. with Dex. in liver "rat donor" was transmissible to "recipient rat" after liver transplantation. Sixty rats were divided in 5 groups. In group T, a single dose of CsA (10 mg/kg) was administered intravenously in 10 rats; in group D, 10 rats were treated with Dex (300 mg/kg daily for 4 days) and then received CsA as above; in group BN 5 rats were treated with beta-naphthoflavone. Thirty five rats underwent a liver transplantation either from "non induced donors" (group G, n = 11) or from "induced donors with Dex." (group GD, n = 24) followed by CsA injection the next day. For each rat, CsA plasma levels were determined by radioimmunoassay in 6 samples. Liver microsomes cyt. from samples of the liver of donor rats (group G and GD) or after sacrifice (group T, D, BN) were quantitated by immunoblot analysis and estimated from densitometric analysis of the blot. Mean maximal plasma concentration (Cmax) were 2,822 +/- 997 ng/ml in group T, 1,447 +/- -458 ng/ml in group D, 2,685 +/- 1,383 ng/ml in group G, 1,337 +/- 713 ng/ml in group GD and 3,094 +/- 685 ng/ml in group BN. Considering the Cmax and the ASC (area under curve), there was a significant difference between all groups and separately between groups T and D, G and GD.(ABSTRACT TRUNCATED AT 250 WORDS)

The risk of cardiac injury during laparoscopic fundoplication: cardiac troponin I and ECG study.

BACKGROUND: Myocardial trauma has been described during gastroesophageal reflux laparoscopic surgery, in association with the proximity of cardiac structures. In addition, specific haemodynamic changes induced by CO2 pneumoperitoneum could exacerbate perioperative cardiac complication even in patients without cardiac risk factors. The aim of this study was to evaluate the influence of gastroesophageal reflux laparoscopic surgery on the perioperative ECG, cardiac troponin I and myocardial enzyme changes. METHODS: Forty-two ASA I-II patients without ischaemic heart disease or combined double-risk factors were studied. Automated ST segment analysis was used intraoperatively. ECG, plasma myocardial enzyme and cardiac troponin I concentrations were reported on arrival in the recovery room (HO), 4 h (H4) and 24 h (H24) postoperatively. RESULTS: Intraoperative ST segment changes occurred in two patients: the first during a hypotensive episode (MAP<55 mmHg; 3/42 patients) and the second during a hypertensive episode (MAP >110 mmHg; 3/42 patients). One case of intraoperative subcutaneous emphysema occurred without ST disturbance. One case of pneumothorax was observed at H0-H4 in another patient without clinical symptoms. Cardiac troponin I and CK-MB were not increased postoperatively. Transaminase concentrations increased (2-fold normal values) in 26/42 patients. In these 26 patients, 7 experienced 5-fold isolated transaminase increase, associated with left hepatic artery section. CONCLUSION: According to perioperative ECG changes and/or specific cardiac troponin I measurements, we did not identify specific myocardial damage following gastroesophageal reflux laparoscopic surgery. Unexpectedly, the incidence of hepatic cytolysis was frequent (62%) and has not previously been reported in the literature.

[Prolonged functional disturbance of prolactin secretion after surgery under neuroleptanalgesia]. / Perturbation fonctionnelle prolongee de la secretion de prolactine apres chirurgie sous neuroleptanalgesie.

Plasma level of prolactin and its response to the injection of haloperidol were measured in nine women before and after elective gynecological surgery under neuroleptanalgesia using dextromoramidedroperidol combination. The day before the operation, the injection of haloperidol 0.25 mg intramuscularly increases the concentration of PRL by 5.4 +/- 1.9 mg/ml, while this response is completely abolished the day following the operation. Two days later, a tenfold increase in the dose of haloperidol (2.5 mg I.M.) is necessary to obtain a PRL response that equals that observed pre-operatively (5.8 +/- 1.2 ng/ml). The low plasma levels observed 24 and 48 hours post-operatively compared to the pre-operative level, illustrate a prolonged functional disturbance of the secretion of PRL.