Estudio de Efecto de Neurotoxicos Sobre Equilibrio

8/13/2019 Estudio de Efecto de Neurotoxicos Sobre Equilibrio

1/9

Industrial Health 2002, 40 , 1422

*To whom correspondence should be addressed.

Original Article

Computerized Posturography with Sway FrequencyAnalysis: Application in Occupational andEnvironmental Health

Kazuhito YOKOYAMA*, Shunichi ARAKI, Mariko NISHIKITANI, and Hajime SATO

Department of Public Health and Occupational Medicine, Graduate School of Medicine/Faculty of Medicine,The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan

Received April 14, 2001 and accepted September 20, 2001

Abstract: To examine the effects of occupational and environmental neurotoxicants on vestibular,

cerebellar and spinocerebellar functions, the following three groups of subjects were examined, usinga computerized posturography with sway frequency analysis: (1) 49 male chemical factory workersexposed to lead stearate, aged 2763 (mean 43) years, with concurrent blood lead concentrations (BPbs)of 11113 (mean 48) g/100 g and past mean BPbs of 752 (mean 24) g /100 g; (2) 29 male sandal, shoeand leather factory workers, aged 3573 (mean 51) years, with urinary 2,5-hexanedione (HD)concentrations of 0.413.06 (mean 1.20) mg/g creatinine; and (3) 9 females, aged 19-58 (mean 29)years, who were exposed to sarin accidentally 68 months before the study (Tokyo Subway SarinPoisoning, March 20, 1995) and showed plasma cholinesterase (ChE) activities of 1395 (mean 68) IU/ l on the day of poisoning. The pattern of posturographic changes in lead workers suggested that thevestibulocerebellum (lower vermis), anterior cerebellar lobe and spinocerebellar afferent pathway wereasymptomatically affected; the vestibulocerebellar change reflected concurrent lead absorption andthe anterior cerebellar one reflected past absorption. Similarly, vestibulocerebellar and spinocerebellarfunctions were affected by n-hexane in solvent workers; the effect on the vestibulocerebellar functionwas probably inhibited by xylene. Also, the chronic (long-term) effect on the vestibulocerebellar functionpersisted in acute sarin poisoning. It is thus suggested that the vesitibulocerebellar function is mostsensitive to all the three chemicals examined. It appears that the computerized posturography withfrequency analysis is a useful technique for assessment of vestibular, cerebellar and spinocerebellareffects in occupational and environmental health.

Key words: Computerized posturography with sway frequency analysis, Lead, Organic solvent, Sarin,Vestibular function, Cerebellar function, Spinocerebellar function

purpose 215) . This technique measures displacements of thebodys center of pressure in a horizontal plane (postural sway)by the use of a force platform connected to a microcomputer;summary measures generally used in these studies werelength of the sway path or speed of the sway and the areaincluded within the sway path.

We have recently developed a system of posturography withfrequency analysis of postural sway in our laboratory 1622) .Frequency analysis could be useful in understanding themechanism of neurotoxicity of occupational and

Introduction

Neurobehavioral methods such as neurobehavioral testbat ter ies , neuroelectrophysiological techniques ,neuroimaging and biological markers have been widely usedto examine the effects of various occupational andenvironmental factors on the nervous system 1). Computerizedstatic posturography has also been introduced for this


2/9

15APPLICATION OF POSTUROGRAPHY IN OCCUPATIONAL AND ENVIRONMENTAL HEALTH

environmental factors, as many clinical studies havesuggested that disorders of the vestibular, spinocerebellarafferent, and cerebellar systems are related to changes inspecific frequency domains and directions of posturalsway 2328) . The lesion of the vestibulocerebellum (lower

vermis), which contains the vestibulocerebellar pathway,shows a sway of no specific frequency with eyes open (lowRomberg quotient) (the Romberg quotient is defined as theratio of the value with eyes closed to that with eyes open 24)).The lesion of the spinocerebellar afferent pathway (includingthe spinocerebellar tract and proprioceptive nerve fibers inthe legs) is associated with an omnidirectional sway of lowfrequency (1 Hz or less) with eyes closed (high Rombergquotient). The lesion of the anterior cerebellar lobe is relatedto a sway of high frequency (24 Hz) predominantly in theanteroposterior direction with eyes closed (high Romberg

quotient).In this paper, we reexamine our recent findings oncomputerized posturography with frequency analysis insubjects exposed to lead, organic solvents and sarin 1622) toclarify which of the vestibulocerebellar, spinocerebellar andanterior cerebellar lobe function is most affected by thesechemicals.

Subjects and Methods

Subjects

Three groups of subjects (exposed-groups) were examined,i.e., 49 male lead workers, 29 male solvent workers, and 9female sarin-poisoning patients, together with controlsubjects for each group, consisting of 23 males, 22 malesand 18 females, respectively 1622) . Age, height, body weight,alcohol consumption and exposures for the exposed-groupsand controls are shown in Table 1. There were no significantdifferences in age, height, body weight, or alcoholconsumption between the lead workers, solvent workers orsarin poisoning patients and their controls (p>0.05). It wasconfirmed by interviews by one of the authors that none of

control subjects had been exposed to neurotoxic agents suchas heavy metals and organic solvents. Similarly, none of exposed-groups had been exposed to neurotoxic chemicalsother than lead, organic solvents and sarin, respectively; theyshowed no specific signs or symptoms indicative of clinicalpoisoning or of neurological, endocrinological, or mentaldisorders at the time of the study. The nature of the procedurewas fully exposed to all subjects and the study was conductedwith their informed consent.

The followings are brief description of exposed-groups:Lead workers: This group consisted of workers, who had

been worked at a chemical factory producing lead stearate.Records of BPb concentrations were available for 27 yearsbefore the study (past BPbs); maximum values of BPb(MaxBPb), mean values (MeanBPb), and cumulative values(CumBPb) were calculated (Table 1).

Solvent workers: This group were artisans, who had beenengaged in making sandal, shoe, and leather at small factoriesusing solvent mixtures containing mainly n-hexane, xylene,and toluene. Concentrations of metabolites of solvents inurine samples taken from the workers in the morning beforework for 2,5-hexanedione (HD), methylhippuric acid (MHA),and hippuric acid (HA) (Table 1) were higher than those of male Japanese without solvent exposure, i.e., 0.25 0.23mg/g Creatinine (Cn) for HD, 0.028 0.021 g/g Cn for MHA,and 0.14 0.71 g/g Cn for HA, respectively (mean SD) 29, 30) .HD in end-of-shift urine of workers was estimated to be at

least twice that in the samples examined, i.e., about 0.86(mean 2.4) mg/g Cn, as urinary samples were takenapproximately 16 hr after the end of last shift (17:00) andthe half-life of urinary excretion of HD is 1314 hr 31). Thesevalues may correspond to 13100 (mean 40) ppm of n-hexanein air during work, as it has been reported that 3 mg/g Cn of HD in end-of-shift urine is equivalent to 50 ppm of n-hexanein air 32). Similarly, MHA concentrations in urine of the workersat the end of shift were estimated at approximately 519 foldsof those in the morning urine, i.e. 0.953.6 g/g Cn on average,considering its half-life time (3.87.1 hrs) 33); these estimated

values of MHA might be converted to 46176 ppm of xylenein air as it was reported by Ogata and Taguchi (1986) 34) that2.05 g/g Cn of MHA corresponds to 100 ppm of xylene. HA,of which half-life is 6.3-6.8 hours 33), in the end-of-shift urinecould be 56 folds of that in the morning urine, i.e. 1.92.2g/g Cn on average, which corresponds to 7993 ppm of toluenein air according to the relationship given as a figure in theOgata and Taguchis report 34).

Sarin poisoning patients: This group were females exposedto sarin accidentally in subways in Tokyo, Japan, on March20, 1995. They were transported to St. Lukes International

Hospital to receive emergency medical checks and treatment just after the poisoning. On admission to the hospital, plasmacholinesterase (ChE) activities (Table 1) were lower thannormal range (100250 IU/l). Their major signs andsymptoms were dyspnea and headache in 6 cases, nausea,feeling of asthenia, diplopia and ocular pain in 4, vomitingin 2, and sneezing, paresthesia, cough, loss of consciousness,and heart arrest in 1. They were examined in September toNovember 1995, i.e. 68 months after the poisoning. PlasmaChE activities were measured again on the days of the study,and all were found to be within normal range.


3/9

16 K YOKOYAMA et al.


Computerized static posturographyPostural balance was quantitatively measured by the

method reported previously by us 1622) . Measurement was

conducted in a quiet room with flat floor by the use of astrain-gauge-type force platform (Static Sensograph 1G06,NEC Sanei, Tokyo) connected to a microcomputer (PC9801,NEC, Tokyo) via an analog-to-digital converter (ANALOGPRO, Canopus, Tokyo). Subjects were instructed to refrainfrom alcohol or drugs from the day before the study (12hours or more prior to the study).

Subjects were asked to stand quietly on the platform for60 seconds with eyes open and then for 60 seconds witheyes closed. The medio-lateral (right-left) and anteroposteriorlocation of the bodys center of pressure (CP) in the horizontal

plane was recorded at a sampling frequency of 20 Hz.Displacements of the bodys CP in the both directions werethen subjected into the Fast Fourier Transformation

analysis18, 24)

. The total duration of sampling was 51.2 secas 1024 points (60 sec as 1200 points in lead case). Thespan of frequencies analyzed ranged from 0 to 4 Hz (0.02Hz steps). Sum of the root squares of the power calculatedfrom the power spectrum between (1) 0 and 1 Hz, (2) 1 and2 Hz and (3) 2 and 4 Hz [(1) 0.02 and 0.125 Hz, (2) 0.125and 0.25 Hz, (3) 0.25 and 0.5 Hz, (4) 0.5 and 1 Hz, (5) 1 and2 Hz, and (6) 2 and 4 Hz in lead wokers] served as measuresof the amount of postural sway for each frequency rangewith eyes open and closed. Also, length of displacement of the CP in the medio-lateral and anterior-posterior directions

Table 1. Age, height, body weight, biological exposure indices and exposure length in subjects exposed tolead (lead workers), organic solvents (solvent workers) and sarin (sarin-poisoning patients) and their controls

Exposed Controls

Lead:N 49 23

Age (years) 48.2 9.0 (2763) 46.7 12.0 (2965)

Height (cm) 164.6 3.9 (156172) 166.2 3 .6 (159172)Body weight (kg) 62.7 7.9 (4980) 63.1 9.1 (4677)Alcohol consumption (ml/week) 205 159 (0539) 132 1 65 (0567)BPb ( g/100g) 18 6.7 (736) MaxBPb ( g/100g) 48 26.7 (11113) MeanBPb ( g/100g) 23.5 9 .1 (7.351.6) CumBPb ( gyears/100g) 390.6 337.6 (14.71267.8) Exposure length (years) 14.5 9.7 (234)

Organic solvents:N 29 22Age (years) 50.6 7.3 (3573) 49.3 7.0 (3365)Height (cm) 162.6 6.4 (153176) 165.7 16.0 (154176)Body weight (kg) 61.0 8.8 (4479) 62.1 16.8 (4673)Alcohol consumption (ml/week) 160.6 171.7 (0700) 198.9 466.1(0749)HD (mg/g creatinine) 1.20 0.59 (0.413.06) HA (g/g creatinine) 0.37 0.48 (0.052.53) MHA (g/g creatinine) 0.19 0.08 (0.100.43) Exposure length (years) 27.6 9.9 (342)

Sarin:N 9 18Age (years) 29.4 12.1 (1958) 35.1 7.8 (2347)Height (cm) 158.2 3.6 (153163) 156.3 1 .9 (154161)Body weight (kg) 47.7 1.9 (4550) 50.3 4.5 (4561)

Alcohol consumption (ml/week) 25.2 39.4 (0123) 60.5 105.9(0400)ChE (IU/l) 68.2 29.8 (1395)

Average standard deviation with range in parenthesis. BPb = Concurrent blood lead concentration, MaxBPb= Maximum blood lead concentration in the past, MeanBPb = Mean blood lead concentration in the past,CumBPb = MeanBPb X exposure length; HD, HA and MHA = Urinary concentrations of 2,5-hexanedione,hippuric acid and methylhippuric acid; ChE = Plasma cholineesterase activity.


4/9


within each sampling time were summed up for each directionand defined as the length of sway path of the bodys CP inthe medio-lateral (Dx) and anteroposterior (Dy) directions,respectively; and area included within the sway path traveledby the CP during 60 sec (Area) was calculated.

Statistical analysisDifferences in Dx, Dy, Area, and power of the sway for

each frequency range with eyes open and closed betweenthe lead workers, solvent workers, or sarin-poisoning patientsand their controls were examined by analysis of covarianceto control for possible confounding effects of age, height,body weight, and alcohol consumption 7, 12) by assigning thesevariables as covariates. Relations of postural sway parametersto concurrent BPb, MaxBPb, MeanBPb and CumBPb (leadworkers), HD, MHA, and HA (solvent workers), and ChE

activities on the day of the poisoning (sarin-poisoningpatients) were examined by multiple regression analysis.All the statistical analyses were performed by SPSS ver.4.0 35)

using a microcomputer (Mac IIVx, Apple).

Results

Differences in power spectrum of postural swayfrequencies between lead workers, solvent workers or sarin-poisoning patients and their controls are shown in the Fig.1. Those in Dx, Dy and Area are shown in Table 2. Results

obtained for each group of subjects are as below.

Lead workersWith eyes open, the Dx, Area, and power of the sway of

0.1250.25 and 0.51 Hz and high frequency 24 Hz in themedio-lateral direction and of the 0.250.5 Hz sway in theanteroposterior direction were significantly increased. Thus,there was an increase in the postural sway of thevestibulocerebellar type, i.e., omnidirectional sway of nospecific frequencies with eyes open in lead workers. Witheyes closed, power of the 0.251 and 24 Hz sway in the

medio-lateral direction was significantly increased in leadworkers as compared with controls, indicating that the swayof the spinocerebellar and cerebellar anterior lobe types,respectively, were significantly increased.

In the multiple regression analysis controlling for age,height, body weight and alcohol consumption, with eyesopen, power of the 0.51 and 12 Hz sway was positivelyre la ted to concur ren t BPb (pa r t i a l r eg ress ioncoefficients=0.32 and 0.31, respectively, p


5/9



The observation that the vestibulocerebellar sway isaffected by n-hexane is compatible with the data in rats thathistopathological changes (distal axonal swelling and

degeneration) were caused by n-hexane in the vermis 36, 37) ,which contains the vestibulocerebellum (lower vermis).Similarly, the observation of the increase in the

Fig. 1. Differences in power spectrum of postural sway frequencies (mean values and standard errors) between49 lead workers and 23 controls (top), 29 solvent workers and 22 controls (center) and 9 sarin-poisoning patientsand 18 controls (bottom) examined by analysis of covariance. *p


6/9


less than the estimated level in the present studyi.e. 20ppmof n-hexane 31). Indeed, we have already reported thechanges in autonomic function (electrocardiographic R-Rinterval variability) in the same group of workers as thepresent study 38) .

On the other hand, as location of histopathological changesin the cerebellum (perivascular periodic acid-Schiff-positiveexdaute, extracellular edema, focal necrosis of neurones andglias) has not been specified in previous studies on humanlead poisoning 3942) , it seems difficult to explain the functional(subclinical) changes in postural sway presented here bythe histopathological findings obtained in the studies on leadpoisoning. Also, neuronal degeneration and necrosis in brainincluding the cerebellum (vermis), similar to those in hypoxicencephalopathy, which have been observed in rats survivingconvuls ions af ter in ject ion of soman [o-(1,2 ,2-

t r i m e t h y l p r o p y l ) - m e t h y l f l u o r o p h o s p h a t e ] ( aorganophosphate compound which is strongly toxic likesarin) 43, 44) , could not explain the changes in postural swayin sarin poisoning patients, because hypoxic damage to brainwas doubtful in the sarin cases as convulsion was not observedin the cases (only one case showed cardiac arrest).Histopathological changes underlying the effects of lead andsarin on postural balance remain to be investigated.

In lead workers, MaxBPb showed an unexpected inverserelation to the sway parameters in the multiple regressionanalysis, possibly due to a mere chance caused by controlling

for many variables in the multiple regression analysis. It issuggested that concurrent BPb and MeanBPb rather thanMax BPb have significant effects on postural balance.Furthermore, our study suggested that the possibility thatxylene can inhibit the effect of n-hexane on postural balance,i.e. the vestibulocerebellar type of sway was inversely relatedto MHA, denying adverse effect xylene, which has beenknown as a neurotoxic substance 37, 4547) . This coincides withthe observation that n-hexane-induced slowing of peripheral

Table 2. Differences in postural sway between 49 lead workers and23 controls, 29 solvent workers and 22 controls, and 9 sarin-poisoningpatients and 18 controls a

Cases Controls

Lead workersEyes open:

Dx (cm) 54.8 (30.8104.4) 46.8 (21.368.6)Dy (cm) 48.7 (28.388.6) 43.6 (25.768.7)Area (cm 2) 3.1 (1.06.3) 2.5 (0.85.77)

Eyes closed:Dx (cm) 66.3 (2.7111.2) 63.2 (30.391.9)Dy (cm) 63.5 (24.7189.0)* 57.3 (28.584.4)Area (cm 2) 3.6 (0.18.8)* 3.3 (1.26.5)

Solvent workersEyes open:

Dx (cm) 48.3 (27.068.0)* 46.1 (21.368.6)Dy (cm) 42.2 (24.899.1) 42.5 (25.768.7)Area (cm 2) 3.0 (1.18.1)* 2.5 (0.785.73)

Eyes clesed:Dx (cm) 78.4 (42.1165.7) 61.8 (30.386.4)Dy (cm) 75.5 (30.9143.9) 56.8 (28.584.4)Area (cm 2) 4.9 (1.210.0) 3.4 (1.26.5)

Sarin poisoning patientsEyes open:

Dx (cm) 45.1 (26.376.2) 44.2 (29.467.8)Dy (cm) 32.0 (21.348.4) 35.1 (23.455.4)Area (cm 2) 2.7 (1.15.0)* 2.1 (0.73.2)

Eyes clesed:Dx (cm) 60.4 (30.8103.6) 61.4 (34.592.7)Dy (cm) 45.0 (26.870.2) 47.5 (27.173.9)Area (cm 2) 4.0 (1.87.1) 3.4 (1.29.2)

Average with range in parenthesis. aLead workers, solvent workers andtheir controls are males; the remainings are females. *p


7/9



nerve conduction and prolongation of latencies of visualevoked potentials are inhibited by xylene in rats 48) . Bycontrast, mixed absorption of n-hexane and xylene inducesan enhanced loss of auditory sensitivity (click exposure) ascompared with mono-exposure to n-hexane in rats 46) .

Therefore, interaction between these solvents on the nervoussystem may depend on the target; co-exposure to xylenedoes not imply reduction of the risk of n-hexane as healthhazard on workers. In our study no significant effects of toluene were demonstrated in the regression analysis. Effectsof co-exposure of these solvents and their interactions shouldbe investigated further.

In contrast to the results on sarin poisoning patients, thestudy on pesticide applicators 11) with concurrent exposureto organophosphate showed that postural balance expressedby a total length of the sway path was affected more greatly

with eyes closed than with eyes open. The discrepancybetween the two studies also remains unexplained.Thus, a static posturography with frequency analysis of

postural sway is demonstrated to be useful for assessingdose-effect relationships between neurotoxic chemicals suchas lead, organic solvents and sarin, and their effects onpostural balance systems, in light of results from previousstudies 215) which revealed significant increase in the posturalsway caused by chemical substances. However, there aresome weaknesses in the studies presented here. First,smoking status was not surveyed. Though some studies

reported that smoking has no significant effects on posturalbalance 11, 15) , there are also reports that smoking increasespostural sway 49) . Second, as some subjects reported heavyconsumption of ethanol in the study on solvent workers, itsinteraction with solvent exposure should have been examined.Similarly, BPb concentrations in the lead workers study andages in the sarin patients study showed a substantial variation;more strict controls in demographic variables should bepreferable. To confirm the findings on effects of variouschemicals on postural balance system further, examinationon the vestibulo-oculomotor system such as optokinetic

nystagmus test as well as investigation on the brainstemsuch as measurement of brainstem auditory evoked potentialsshould be useful.

Acknowledgments

We wish to thank Dr. Katsuyuki Murata for his technicalcollaboration.

References

1) Araki S (ed), Gilioli R, Landrigan PJ, Yokoyama K(Assoc eds) (1994) Neurobehavioral methods inoccupational and environmental health. 11020,

Academic Press, New York. 2) Bhattacharya A, Shukula R, Bornschein R, Dietrich K,Kopke JE (1988) Postural disequilibrium in childrenwith chronic lead exposure: a pi lot s tudy.NeuroToxiology 9, 32740.

3) Antti-Poika M, Ojala M, Matikainen E, Vaheri E,Juntunen J (1989) Occupational exposure to solventsand cerebellar, brainstem and vestibular functions. IntArch Occup Environ Health 61, 397401.

4) Ledin T, Odkvist L, Moller C (1989) Posturographyfindings in workers exposed to industrial solvents. Acta

Otolaryngol (Stockh) 107 , 35761. 5) Moller C, Odkvist L, Thell J, Larsby B, Hyden D,Bergholtz, L, Tham R (1989) Otoneurological findingsin psycho-organic syndrome caused by industrial solventexposure. Acta Otolaryngol (Stockh) 107 , 512.

6) Bhattacharya A, Shukula R, Bornschein R, Dietrich K,Keith R (1990) Lead effects on postural balance of children. Environ Health Perspect 89 , 3542.

7) Dick RB, Bhattacharya A, Shukla R (1990) Use of acomputerized postural sway measurement system forneurobehavioral toxicology. Neurotoxicol Neuroteratol

12 , 16. 8) Moller C, Odkvist L, Larsby B, Tham R, Ledin T,Bergholtz L (1990) Otoneurological findings in workersexposed to styrene. Scand J Work Environ Health 16,18994.

9) Linz DH, Barrett ET Jr, Pflaumer JE, Keith RE (1992)Neuropsychologic and postural sway improvement afterCa++ EDTA chelation for mild lead intoxication. J OccupMed 34 , 63841.

10) Bhattacharya A, Shukula R, Dietrich K, Miller J,Bagchee A, Bornschein R, Cox C, Mitchell T (1993)

Functional implications of postural disequilibrium dueto lead exposure. NeuroToxicology 14, 17990.11) Sack D, Linz D, Shukula R, Rice C, Bhattacharya A,

Suskind R (1993) Health status of pesticide applicators:postural stability assessment. J Occup Med 35, 1196202.

12) Chia SE, Chua LH, Ng TP, Foo SC, Jeyaratnam J (1994)Postural stability of workers exposed to lead. OccupEnvion Med 51 , 76871.

13) Kilburn KH, Warshaw RH, Hanscom B (1994) Balancemeasured by head (and trunk): tracking and a force


8/9


platform in chemically (PCB and TCE) exposed andreferent subject. Occup Environ Med 51 , 3815.

14) Chia SE, Chia HP, Ong CN, Jeyaratnam J (1996)Cumulative concentrations of lead and postural stability.Occup Envion Med 53 , 2648.

15) Kuo W, Bhattacharya A, Succop P, Linz D (1996)Postural stability assessment in sewer workers. J OccupEnviron Med 38, 2734.

16) Araki S, Murata K, Yokoyama K (1994) Applicationof neurophysiological methods in occupational medicinein relation to psychological performance. Ann AcadMed Singapore 23, 7108.

17) A r a k i S , Yo k o y a ma K , M u r a t a K ( 1 9 9 7 )Neurophysiological methods in occupational andenvironmental health: methodology and recent findings.Environ Res 73 , 4251.

18) Yokoyama K, Araki S, Murata K, Nishikitani M,Nakaaki K, Yokota J, Ito A, Sakata E (1997) Posturalsway frequency analysis in workers exposed to n-hexane, xylene, and toluene: Assessment of subclinicalcerebellar dysfunction. Environ Res 74 , 1105.

19) Yokoyama K, Araki S, Murata K, Morita Y, KatsunoN, Tanigawa T, Mori N, Yokota J, Ito A, Sakata E (1997)Subclinical vestibulo-cerebellar, anterior cerebellar lobeand spinocerebellar effects in lead workers in relationto concurrent and past exposure. NeuroToxicology 18,37180.

20) Yokoyama K, Araki S, Murata K, Nishikitani M,Okumura T, Ishimatsu S, Takasu N (1998) A preliminarystudy on delayed vestibulo-cerebellar effects of Tokyosubway sarin poisoning in relation to gender difference:Frequency analysis of postural sway. J Occup EnvironMed 40, 1721.

21) Yokoyama K, Araki S, Murata K, Nishikitani M,Okumura T, Ishimatsu S, Takasu N (1998) Chronicneurobehavioral and central and autonomic nervoussystem effects of Tokyo subway sarin poisoning. JPhysiol (Paris) 92 , 31723.

22) Araki S, Sato H, Yokoyama K, Murata K (2000)Subclinical neurophysiological effects of lead: a reviewon peripheral, central, and autonomic nervous systemeffects in workers. Am J Ind Med 37 , 193204.

23) Mauritz KH, Dichgans J, Hufschmidt A (1979)Quantitative analysis of stance in late cortical cerebellaratrophy of the anterior lobe and other formas of cerebellar ataxia. Brain 102 , 46182.

24) Diener HC, Dichgans J, Bacher M, Gompf B (1984)Quantification of postural sway in normals and patientswith cerebellar diseases. Electroencephal Clin

Neurophysiol 57 , 13442.25) Yagi K (1989) Multivariate statistical analysis in

stabilometry in human upright standing (the first report):age-related factor. Jap J Otorhinolaryngol 92, 899908(Japanese with English abstract).

26) Fitzpatrick RC, Gorman RB, Burke D, Gandevia SC(1992) Postural proprioceptive reflexes in standinghuman subjects: bandwidth of response and transmissioncharacteristics. J Physiol 458 , 6983.

27) Dickgans J, Fetter M (1993) Computerized cerebellarfunctions upon the stabilization of body posture. RevNeurol 149 , 65464.

28) Asahina M, Nakajima M, Kojima S, Hirayama K (1994)Postural sway in patients with hereditary ataxia. RinshoShinkeigaku (Clinical Neurol) 34, 110510 (Japanesewith English abstract).

29) Kawai T, Yasugi T, Mizunuma K, Horiguchi S, UchidaY, Iwami O, Iguchi H, Ikeda M (1991) Dose-dependentincrease in 2,5-hexanedione in the urine of workersexposed to n-hexane. Int Arch Occup Environ Health63, 28591.

30) Kawai T, Yasugi T, Mizunuma K, Horiguchi S, IguchiH, Uchida Y, Iwami O, Ikeda M (1992) Comparativeevaluation of urinalysis and blood analysis as meansof detecting exposure to organic solvents at lowconcentrations. Int Arch Occup Environ Health 64, 22334.

31) IPCS (1991) n-Hexane, Environmental HealthCriteria 122, WHO, Geneva.32) Mutti A, Falzoi M, Lucertini S, Arfini G, Zignami M,

Lombardi S, Franchini I (1984) n-Hexane metabolismin occupationally exposed workers. Br J Ind Med 41,5338.

33) Ikeda M, Hara I (1980) Evaluation of the exposure toorganic solvents by means of urinalysis for metabolites.Jap J Ind Health 22 , 317.

34) Ogata M, Taguchi T (1986) Quantitative analysis of urinary glycine conjugates by high performance liquid

chromatography: excretion of hippuric acid andmethylhippuric acids in the urine of subjects exposedto vapours of toluene and xylenes. Int Arch OccupEnviron Health 58 , 1219.

35) SPSS Inc (1990) SPSS Reference Guide, SPSS Inc.,Chicago.

36) Schaumburg HH, Spencer PS (1976) Degenerationin central and peripheral nervous systems produced bypure n-hexane: an experimental study. Brain 99, 18392.

37) Spencer PS, Schaumburg HH (1985) Organic solvent


9/9



neurotoxicity: facts and research needs. Scand J Work Environ Health 11 (Suppl), 5360.

38) Murata K, Araki S, Yokoyama K, Yamashita K, OkajimaF, Nakaaki K (1994) Changes in autonomic functionas determined by ECG R-R variability in sandal, shoe

and leather workers exposed to n-hexane, xylene andtoluene. Neurotoxicology 15, 86776.39 Smith JF, McLaurin RL, Nichols JB, Asbury A (1960)

Studies in cerebral edema and cerebral swelling. I.The changes in lead encephalopathy in childrencompared with those in alkyl tin poisoning animals.Brain 83, 41127.

40) Popoff N, Weinberg S, Feign I (1963) Pathologicobservations in lead encephalopathy. Neurology 6, 26678.

41) Pentschew A (1965) Morphology and morphogenesis

of lead encephalopathy. Acta Neuropathol 5, 13360.42) Clasen RA, Hartman JF, Starr AJ, Coogan PS, PandolfiS, Laing I, Becker R, Hass GM (1974) Electronmicroscopic and chemical studies of the vascularchanges and edema of lead encephalopathy: acomparative study of the human and experimentaldisease. Am J Pathol 74, 21533.

43) Lemercier G, Carpentier P, Sentac-Roumnou H, MorelisP (1983) Histological and histochemical changes in

the central nervous system of the rat poisoned by anirreversible anticholinesterase organophosphoruscompound. Acta Neuropathol 61 , 12329.

44) McLeod CG, Singer AW, Harrington DG (1984) Acuten e u r o p a t h o l o g y i n s o m a n p o i s o n e d r a t s .

Neurotoxicology 5, 538.45) Politis MJ, Shcaumburg HH, Spencer PS (1981)Neurotoxicology of se lected chemicals . In:Experimental and clinical neurotoxicology. eds. bySpencer PS, Shcaumburg HH 61380, Williams &Wilkins, Baltimore.

46) Savolainen K, Riihimaki V, Laine A (1982) Biphasiceffects of inhaled solvents on human equilibrium. ActaPharmacol Toxicol 51, 23742.

47) Lolin Y (1989) Chronic neurological toxicity associatedwith exposure to volatile substances. Human Toxicol

8, 293300.48) Nylen P, Hagman M (1994) Function of the auditoryand visual systems, and of peripheral nerve, in rats afterlong-term combined exposure to n-hexane andmethylated benzene derivatives. II. Xylene. PharmacolToxicol 74, 1249.

49) Iki M, Ishizaki H, Alato H, Starck J, Pyykko I (1994)Smoking habits and postural stability. Am J Otolaryngol15 , 1248.

Estudio de Efecto de Neurotoxicos Sobre Equilibrio

Documents

Transcript of Estudio de Efecto de Neurotoxicos Sobre Equilibrio