Monitorización neurofisiológica intraoperatoria en la cirugía del nervio periférico: descripción técnica y resultados en nuestro centro / Intraoperative neurophysiological monitoring in peripheral nerve surgery: technical description and experience in a centre

Introducción. La monitorización neurofisiológica intraoperatoria ha experimentado un espectacular desarrollo en los últimos 20 años, particularmente en campos como la neurocirugía y la cirugía de raquis. Se ha constituido en una herramienta muy útil en la prevención de daño neurológico durante la cirugía, si bien su utilidad en la cirugía del nervio periférico en el área de traumatología y ortopedia no ha sido constatada. Objetivo. Describir exhaustivamente la técnica de monitorización neurofisiológica intraoperatoria y secundariamente comunicar la experiencia de nuestro centro. Pacientes y método. Estudio descriptivo retrospectivo de 30 casos de cirugía de nervio periférico realizadas en nuestro centro en el período 2009-2013. Descripción pormenorizada de la técnica de monitorización neurofisiológica intraoperatoria utilizada. Resultados. Registramos 13 tumores del nervio periférico, de estos, obtuvimos 11 resultados excelentes y 2 buenos, uno con hipoestesia temporal y otro con recuperación motora casi completa aunque no sensitiva. Registramos 17 casos de lesiones traumáticas, en 6 casos fue necesaria la realización de injerto, en los 11 restantes solo realizamos neurolisis, con recuperación sensitiva y motora completa. Conclusiones. La monitorización neurofisiológica intraoperatoria supone una herramienta útil en la cirugía secundaria de las lesiones del nervio periférico y en la enfermedad tumoral intraneural de dicho nervio (AU)

Introduction. Intraoperative neurophysiological monitoring has experienced a spectacular development in the past 20 years, particularly in the fields of neurosurgery and spine surgery. it has become a useful, almost indispensable, tool in preventing nerve damage during surgery. The aim of this article is to describe the intraoperative technique and analyze its results in the field of peripheral nerve surgery. Objective. To describe the usefulness of a technique in peripheral nerve surgery, the technique used and the experience in a centre. Patients and methods. A retrospective study was conducted on 30 cases of peripheral nerve surgery performed in this centre from 2009 to 2013, using the intraoperative monitoring technique. Results. Of the total of 13 peripheral nerve tumors recorded, there were 11 excellent results and 2 good results, one temporary hypoesthesia and one with almost complete sensory, except for motor, recovery. Traumatic injury was recorded in 17 cases, of which 6 required performing a graft, and the remaining 11 cases only neurolysis was performed, with complete motor and sensory recovery. Conclusions. Intraoperative neurophysiological monitoring is a useful tool in the secondary surgery of peripheral nerve injury and the intraneural tumor pathology (AU)

Intraoperative neurophysiological monitoring in peripheral nerve surgery: Technical description and experience in a centre.

INTRODUCTION: Intraoperative neurophysiological monitoring has experienced a spectacular development in the past 20 years, particularly in the fields of neurosurgery and spine surgery. it has become a useful, almost indispensable, tool in preventing nerve damage during surgery. The aim of this article is to describe the intraoperative technique and analyze its results in the field of peripheral nerve surgery. OBJECTIVE: To describe the usefulness of a technique in peripheral nerve surgery, the technique used and the experience in a centre. PATIENTS AND METHODS: A retrospective study was conducted on 30 cases of peripheral nerve surgery performed in this centre from 2009 to 2013, using the intraoperative monitoring technique. RESULTS: Of the total of 13 peripheral nerve tumors recorded, there were 11 excellent results and 2 good results, one temporary hypoesthesia and one with almost complete sensory, except for motor, recovery. Traumatic injury was recorded in 17 cases, of which 6 required performing a graft, and the remaining 11 cases only neurolysis was performed, with complete motor and sensory recovery. CONCLUSIONS: Intraoperative neurophysiological monitoring is a useful tool in the secondary surgery of peripheral nerve injury and the intraneural tumor pathology.

Determination of a new oral iron chelator, ICL670, and its iron complex in plasma by high-performance liquid chromatography and ultraviolet detection.

ICL670 is a representative of a new class of orally active tridentate selective iron chelators. Two molecules of ICL670 are required to form a complete hexacoordinate chelate Fe-[ICL670]2 with one ferric iron. A simple and rapid HPLC-UV method for the separate determination of ICL670 and Fe-[ICL670]2 in the plasma of iron-overloaded patients is described. Plasma samples were prepared as rapidly as possible, the tubes being kept at 4 degrees C. Plasma proteins were precipitated with methanol. The supernatant was diluted with water and placed on the refrigerated sample rack of an autosampler before injection. The chromatographic separations were achieved on an Alltima C18 column using 0.05 M Na2HPO4 and 0.01 M tetrabutylammonium hydrogen sulfate-acetonitrile-methanol (41:9:50, v/v/v) as mobile phase. The analytes were detected at 295 nm. Calibration and quality control samples were prepared in normal human plasma. The mean accuracy (n=6) over the entire investigated concentration range 0.25-20 microg/ml ranged from 91 to 109% with a coefficient of variation (C.V.) from 4 to 8% for ICL670, and from 95 to 105% with a C.V. from 2 to 20% for the iron complex. The dissociation of the complex during analysis was shown to be marginal. The iron removal from plasma of iron-overloaded patients by free ICL670 during analysis was low. The in vitro iron transfer from the iron pools of iron-overloaded plasma onto ICL670 was shown to be a slow process.

Plasma deproteinization by precipitation and filtration in the 96-well format.

The need for fast bioanalytical methods within the pharmaceutical sector is rapidly growing. Sample preparation is often the bottleneck step. A new approach to increasing sample throughput involves precipitated protein removal by filtration in the 96-well format, thereby eliminating the need for centrifugation and manual handling of individual tubes. The potential for such a new technique has been investigated for the determination of an iron chelator, a highly protein-bound compound (> or =99.5%) in plasma. An analog was used as internal standard. Acetonitrile and plasma were sequentially aspirated, separated by an air gap, using a manual electronic pipettor. They were then dispensed into the channel of an Empore filter PPT plate above the filter, and a slight vacuum was applied. The eluate was collected and diluted prior to injection. The compounds were then separated by reversed-phase chromatography and detected by UV at 295 nm. The chromatographic run time was 6 min. The mean recovery following protein precipitation was 78%, which shows that the technique can apply to a highly protein-bound compound. Replicate quality control samples were prepared in drug-free normal human plasma at four different concentrations. The mean accuracy ranged from 87 to 108% with the CV ranging from 3 to 8%. The described procedure is simple, fast and reproducible. It requires minimal equipment. The time required to prepare a plate manually is only about 20 min. The use of 12-channel repeater pipettors reduces the risk of error and improves productivity. Automation should be an aid to further increasing sample throughput when more than one plate a day is to be prepared.

Practice of solid-phase extraction and protein precipitation in the 96-well format combined with high-performance liquid chromatography-ultraviolet detection for the analysis of drugs in plasma and brain.

C18 Empore 96-well extraction disc plates have been employed for the analysis of three drugs with different polarities in plasma in conjunction with HPLC-UV, rufinamide, ICL670 and an anticonvulsant agent (AA1) in an early stage of development. With the most polar compound (AA1), ion-pair extraction at pH 12 was applied. The method developed for the assay of AA1 in plasma was applied to its determination in brain using an Oasis HLB plate following homogenisation in a pH 7.4 buffer and protein precipitation with NaOH-ZnSO4, thereby saving time for method development. Protein precipitation in the 96-well format with filtration of the precipitate was applied to the determination of ICL670, a highly protein-bound compound (>99.5%), with a good recovery (78%). Reversed-phase chromatography was applied using a short 5 cm column packed with 3 microm particles for the determination of ICL670 and AA1 and two parallel columns (15 cm long) for the determination of rufinamide. The methods were used routinely, one plate per analysis day being processed, resulting in increase in sample throughput and saving in solvents.

Randomized comparative trial of triflusal and aspirin following acute myocardial infarction.

AIMS: To compare the efficacy and tolerability of the antiplatelet agent triflusal with aspirin in the prevention of cardiovascular events following acute myocardial infarction. METHODS AND RESULTS: In this double-blind, multicentre, sequential design study, patients were randomized within 24 h of acute myocardial infarction symptom onset to receive triflusal 600 mg or aspirin 300 mg once daily for 35 days. The primary end-point was death, non-fatal myocardial reinfarction or a non-fatal cerebrovascular event. The incidences of these individual outcomes and urgent revascularization were secondary end-points. The null hypothesis of no difference between treatments in the primary combined end-point was accepted with 80% power after recruiting 2124 validated patients (odds ratio (OR) for failure [95% confidence interval (CI)]: 0.882 [0.634-1.227]). Non-fatal cerebrovascular events were significantly less frequent with triflusal (OR [95% CI]: 0.364 [0.146-0.908]; P = 0.030). There was no significant difference between treatments for death (OR [95% CI]: 0.816 [0.564-1.179]; P = 0.278), non-fatal reinfarction (OR [95% CI]: 1.577 [0.873-2.848]; P = 0.131) or revascularization (OR [95% CI]: 0.864 [0.644-1.161]; P = 0.334). Overall, both drugs were well tolerated, although there was a trend towards fewer bleeding episodes with triflusal; significantly fewer central nervous system bleeding episodes were observed in triflusal-treated patients (0.27% vs. 0.97%; P = 0.033). CONCLUSION: Triflusal and aspirin have similar efficacy in preventing further cardiovascular events after acute myocardial infarction, but triflusal showed a more favourable safety profile. Triflusal significantly reduced the incidence of non-fatal cerebrovascular events compared with aspirin.

The effect of age on the pharmacokinetics of valsartan.

Twelve young (mean age 23 years, range 18-28) and 12 elderly (mean age 76 years, range 65-89) volunteers were given a single oral dose of 80 mg valsartan after an overnight fast. Each group consisted of six male and six female subjects. Mean systemic exposure to valsartan was higher in the elderly when compared with the young (AUC(0-24 h), 52% increase and AUC(0-infinity), 70% increase). Variability, as shown by the coefficient of variation (CV), was larger for the elderly subjects and ANOVA of the log transformed AUC showed a significant difference between the two groups. This difference was largely brought about by five elderly subjects (one male, four females), whose AUC was about 2-fold higher than the rest of the group. For the remaining elderly subjects, plasma valsartan AUC was similar to that observed for the young volunteers. This higher systemic exposure in five of the elderly subjects is not thought to be of clinical relevance when data from the patient population are considered. Other covariates--such as body weight, comedication, creatinine clearance, valsartan kinetics (absorption rate, distribution, and elimination)--did not explain the higher AUC in this subset of the elderly group. Data from the present study were compared with population kinetic data obtained from larger clinical trials including hypertensive patients in all age groups. Using this population approach, there was no difference in the pharmacokinetics of valsartan between male and female patients. Also, a relationship between plasma clearance of valsartan and age was established. The median age of patients in the hypertensive pool was 55 years. For an average 70-year-old patient, plasma clearance of valsartan is predicted to fall by 22% compared with an average 55-year-old. For the population this difference is not sufficient to warrant initial dose adjustment based on age per se. The covariate age, does not completely explain the variability in the pharmacokinetics of valsartan within the general population. The treatment was well tolerated.

Absolute bioavailability of letrozole in healthy postmenopausal women.

Letrozole is a new non-steroidal inhibitor of the aromatase enzyme system. It is currently under development for the treatment of postmenopausal women with advanced breast cancer. Absolute bioavailability of letrozole when given orally as one 2.5 mg film-coated tablet in comparison to the same dose given intravenously as a bolus injection was studied in 12 healthy postmenopausal women. Letrozole absolute systemic bioavailability after p.o. administration was 99.9 +/- 16.3%. Elimination of letrozole was slow. Total-body clearance of letrozole from plasma after i.v. administration was low (2.21 L h-1). The calculated distribution volume at steady state (1.87 L kg-1) suggests a rather high tissue distribution. Biotransformation of letrozole is the main elimination mechanism with the glucuronide conjugate of the secondary alcohol metabolite being the predominant species found in urine. The two study treatments were tolerated equally well.

High-performance liquid chromatography of the aromatase inhibitor, letrozole, and its metabolite in biological fluids with automated liquid-solid extraction and fluorescence detection.

An analytical method for the determination of letrozole (CGS 20,267) in plasma and of letrozole and its metabolite, CGP 44,645, in urine is described. Automated liquid-solid extraction of compounds from plasma and urine was performed on disposable 100-mg C8 columns using the ASPEC system. The separation was achieved on an ODS Hypersil C18 column using acetonitrile-phosphate buffer, pH 7, as the mobile phase at a flow-rate of 1.5 ml/min. A fluorescence detector was used for the quantitation. The excitation and emission wavelengths were 230 and 295 nm, respectively. The limits of quantitation (LOQ) of letrozole in plasma and in urine were 1.40 nmol/l (0.4 ng/ml) and 2.80 nmol/l, respectively. The respective mean recoveries and coefficient of variation (C.V.) were 96.5% (9.8%) in plasma and 104% (7.7%) in urine. The LOQ of CGP 44645 in urine was 8.54 nmol/l (2 ng/ml). The mean recovery was 108% (6.3%). The compounds were well separated from co-extracted endogenous components and no interferences were observed at the retention times of compounds. The sensitivity of this method for letrozole in plasma should be sufficient for kinetic studies in humans with single doses of 0.5 mg and possibly less.

Development, application and comparison of an enzyme immunoassay and a high-performance liquid chromatography method for the determination of the aromatase inhibitor CGS 20,267 in biological fluids.

CGS 20,267 is a new potent and selective, nonsteroidal, oral aromatase inhibitor. For its determination in human plasma and urine, an enzyme immunoassay (EIA) and an HPLC method were developed. The EIA showed good precision and accuracy (intra- and interassay variation between 3.0 and 17.7%, recoveries between 81 and 106%) and a quantitation limit of 0.7 nmol/L. A strong cross reactivity of the antibodies with the hydroxy metabolite of CGS 20,267 (CGP 44,645) was observed. The HPLC method showed a quantitation limit in plasma of 28 and 34 nmol/L for CGS 20,267 and CGP 44,645, respectively. For urine, concentrations down to 180 nmol/L (CGS 20,267) and 210 nmol/L (CGP 44,645) could be measured. A cross check between EIA and HPLC on plasma samples from healthy male volunteers or breast cancer patients treated orally with CGS 20,267 revealed an excellent correlation (slope = 0.934, intercept = 26, r = 0.991). However, the EIA measurements of urine samples yielded 3-25 times higher concentrations than those obtained by HPLC. Further, HPLC analysis revealed the presence of CGS 20,267 and cross-reacting metabolites in urine but not in plasma. Therefore, the EIA can only be used for the determination of CGS 20,267 in plasma samples.

Pharmacokinetics of pirprofen in children with juvenile chronic arthritis.

Pirprofen (100 or 200 mg; Rengasil) was administered to experimental groups of children (children with juvenile chronic arthritis, JCA) and to a control group of children (children without JCA) as a single dose or as repeated doses. The pharmacokinetics of pirprofen in these children were compared to the pharmacokinetic parameter values obtained in healthy volunteers and in elderly arthritic adults receiving 400 mg of pirprofen. The children were examined regularly and laboratory values were determined in order to detect possible side effects. The results demonstrated that the pharmacokinetics of pirprofen were similar for children and adults when taking into account the dose and the body weight. There was no drug accumulation after repeated administration of pirprofen. As already observed in rheumatic adults, pirprofen remains in synovial fluid longer than in plasma.

High-performance liquid chromatographic determination of pirprofen and five of its metabolites in human plasma without hydrolysis and in human urine before and after chemical hydrolysis.

Selective high-performance liquid chromatographic methods for the simultaneous determination of pirprofen and five of its metabolites either in plasma or in urine before and after chemical hydrolysis were developed. After addition of an internal standard and a buffer, the compounds were extracted from plasma using reversed-phase C18 Bond-Elut columns and from urine using pre-packed silica Extrelut 1 columns, back-extraction into sodium hydroxide and acidification of the alkaline phase before injection. Pirprofen, its five metabolites and the internal standard were separated using a linear elution gradient chromatographic system and wavelength programming. The analysis of spiked samples demonstrated the good accuracy and precision of the methods with limits of quantitation of 100 or 200 ng/ml for the different compounds in plasma, 200 or 360 ng/ml in urine without hydrolysis and 1 or 1.8 micrograms/ml in urine after chemical hydrolysis.

Determination of the (+)- and (-)-enantiomers of pirprofen in human plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method was developed to determine the (+)- and (-)-enantiomers of pirprofen, an anti-inflammatory drug. After addition of an internal standard, the plasma sample was brought onto a glass column pre-packed with silica and eluted with dichloromethane. The extracts were derivatized with 1,1'-carbonyldiimidazole and R (+)-1-methylbenzylamine to form the two diastereomeric amides. The diastereoisomers were separated on a chiral column by HPLC with ultraviolet detection at 272 nm using n-hexane-dichloromethane (64:36, v/v) as the mobile phase. The limit of quantitation was 0.992 mumol/l (0.25 microgram/ml) for each enantiomer.

Simultaneous determination of pirprofen and its metabolite, the pyrrole derivative, in plasma by high-performance liquid chromatography.

A method for the simultaneous determination of pirprofen and its metabolite, the pyrrole derivative, in human plasma is described. The two compounds and the butyric acid analogue of the pyrrole derivative used as internal standard are extracted from plasma with chloroform, then back-extracted into an alkaline buffer. After addition of acid, the aqueous phase is assayed by high-performance liquid chromatography using a fixed-wavelength ultraviolet detector at 254 nm. The limit of quantitation is 0.1 micrograms/ml (0.396 mumol/l for pirprofen and 0.400 mumol/l for the pyrrole derivative).

GLC determination of phenylbutazone in human plasma.

A GLC method for phenylbutazone at concentrations down to 10 ng/ml in human plasma is described. After addition of an internal standard, phenylbutazone is extracted at pH 5 into benzene. The dry extract is dissolved in benzene, and phenylbutazone is determined by GLC using a 63Ni-electron-capture detector.