Document bBDerzbo2V5ZnwGmRMZaBb0YO

D R A F T THE EFFECT OF TNORSAKIC SAD UPON THE COHDUOTIGN VELOCITY OF THE PERIPHERAL NERVES OP RATS AND POPS Medical Research Pro.lect No* MR* Among the Insidious effects of l^organlo lead iq>on animal tissue Is Its action upon peripheral neuromuscular structures. In lead poisoning clinical evidence of neuromuscular Involvement may he absent} when present, it may vary from a mild weakness to paralysis of the musculature affected. "WriBt*drap or paralysis of other muscles may be foreshadowed by gradual weakening or may occur without any premonitory symptoms end generally uapreeeded by pain. The parts frequently affected ere the extensors of the fingers, thumbs end wrists, but the muscles of the leg or feet ere often attacked, sometimes the. back, and q in rare forms of poisoning the muscles of tie eyes" (Hutton,' 1925). Although , Qm &i , fkwehrw hM<te$ 'a &v n .#?**. u Way lead-exposed workers seldom develop muscular paralysis (1), any individual cvum frKtmmc. is A I wtth\am~$Mtfti^wMMwge}fc^ of this paralysis. | The sits of this deleterious action of lead on the neuromuscular system / has hot been definitely established (5, 8), The demonstration of segmental demyelination of nerves from lead-poiaoned guinea pigs (5) indicates, however, that the muscular paralysis Isfc- at-leai^--i-part'ii secondary to disturbances in the conduction ot{tmvq> inpulses^^*( the musculature affected, A physiological method for detecting peripheral nerve damage is the measurement of impulse conduction velocity between two points along a nerve trunk, a technique undergoing extensive clinical trial. Impulse conduction velocity is decreased in the area of a local compression lesion (11), in many cases of acute polyneuritis (2, 11), which finding may differentiate this condition from acute poliomyelitis (11), and in diabetes mellitus (3, 6, 12, 13, 13, 19). There have been several reports of slowed conduction along the ulnar nerve attributed to industrial poisons. These include 15 patients with occupa* tional lead poisoning without neurological symptoms (17) end ten women with N37529 2 severe polyneuropathy associated with chronic triorthocresyl phosphate poisoning (16). In addition, "borderline" slowing was observed In two patients with lead neuropathy and in five with neuropathy due to the cutaneous absorption of an industrial solvent* (18). Animal experiments correlate slowed conduction velocity with clinical, and sometimes histological, evidence of nerve damage: in allergic polyneuritis in guinea pigs (10), in diphtheric polyneuritis in cats (It) and guinea pigs (10), in alloxan diabetes in rats (b) end, with histological eon* firaatlon, lead poisoning in guinea pigs (5). tn view of the clinical and experimental evidence correlating nerve damage with slowed conductiodyelooity, the use of velocity measurements for detecting peripheral nerve injury is promising, it was decided, therefore, to measure the conduction velocities of excised nerves, available at autopsy, from the rats' sad dogs In the 2yesar lead feeding study, c *.i ::x l'-', 'v ft ,: , METHODS ^ $'\>>-#* | a .d* In principle, measurement of the impulse conduction velocity of an excised nerve fiber is straightforward, requiring only the measurement of the time it takes for the impulse to travel from one point of the fiber to another. If the distance between the two points is known, the velocity can be calculated, in practice, one end of the fiber is stimulated by passing an electric current through a short section, 3 to J mo, between two electrical contacts, the A stimulating electrodes, -She- minute change in the membrane potential, known as the action potential, vgaMr is associated with the Impulse as it travels along tU> '* vtuw-ms the fibers dateoWl^by another electrical contact, the recording electrode| * 85?6 trichlorethylane, 10$ ethylene diehloride, 5$ tritoluol phosphate. DUP050044155 3 sidUA . amplifie<^.and fed Into a, sensitive recording device, usually a cathode ray // oscilloscope. In the present experiments, a nerve trunk containing many fibers was studied, Adequate "maximal'1 stimulation of a nerve trunk initiates impulses in all of the fibers j each impulse is conducted along its fiber at a rate hftju. characteristic of that fiber, rapidly in some,^ slowly in others* The action potentials associated with the successive arrivals of the Impulses at the recording electrode causa a sustained, sometimes complex, deflection of the oaeilioeecpe beam called the "compound" action potential* At any selected point of thejoecilloflcope tracing, the magnitude of the deflection is a function of the number of Impulses at the recording electrode at that particular instant. X* Equipment: Figure 1 la a photograph of the equipment need in the experiments. From left to right in the photograph are l) the constant temperature shelter in the right portion of which an electrode set is visible, 2) the tele*^theimciaeter, 5) the stimulus Isolation unit, 4) the recording unit consisting of amplifier and oseiUoscqps, and 3) the Tektronix stimulation unit* A. Electrodes* Two electrode sets, ons for dog nerves and.a smaller one for rat, vara daalpsd by Paul E. Smith, Jr., mod made by Edvard ? Fabryka, of the Physics Section* Each set consists of a holder aada from l/MmCh Teflon sheet supporting a horizontal row of equally spaced and parallel platinum vires (Fig. 2). The first two vires at one and of the row serve as the stimulating electrodes, Si, 8a; any two of the other vires may serve as recording electrodes? r , (Two are necessary to cooplete the circuit through the recording device.) * In addition to the stimulating electrodes, the small holder has nine recording electrodes spaced every 5 mm} maximum available conduction distance: 4 cm. The large holder has 20 recording electrodes spaced 10 mm apart, maximum conduction distance: 18.5 cm. In addition, the large set has "dummy" vires between electrodes to give added support to the nerve and minimise sagging. DUP050044156 k B. Stimulator, In tbs earlier experiments a (braes square wave stimulator, Model 840 was used. It was replaced by a Tektronix unit assembled by Paul E, Smith, Jr. j it consists of a pair of Type 161 pulse generators each driven by a Type 152 Wave-form generator* Bth stimulators provide a stimulus which csn be controlled as to duration, voltage, and frequency of implication. The strength of the stimulus applied to a nerve was 4 to 10 volts and its duration was 0,06 to 0.1 mSec (milliseconds)* In order to minimise the effect of the stimulus current upon the oscilloscope beam, an isolation unit, "3" in Figure 1, was placed in the Stimulation circuit between the stimulator e) lft L and the nerve: a Grass SHJwB Attsolation unit with the Grass stimu- (S^ ^ lator end an Argonaut LIT 069 isolation transformer with the Tektronix, g/ C, Becording Equipment, Tektronix units were used. The nerve action potentials were amplified by a differential amplifier, Type 2A63, or Type JA3 Dual Traced, and fed into a Type 56lA cathode ray oscilloscope. The sweep of the oscilloscope beam was triggered by a mechanism within the stimiUtorH%^r^W"-^ jamM^tbe speed of the sweep was controlled by a Type 2B67 time base Which has a range of 1 microsecond to 3 seconds per screen division, <> The oscilloscope tracing was photographed with a Tektronix C 12 camera unit using Polaroid Type 410 black and white land film* Measurements were made directly from the photographs. * Amplification range: Type 2A63: 20 volts to 1 millivolt pef screen division. Type 3A3: 10 volts to 0.1 millivolt per screen division. DUP050044157 3 Constant Tennerature Shelter. During experiments nerves .nut remain #V moist/ in addition, mammalian name nut be kept at body temperature, A 37C (98.6P), if conduction velocities are to be equivalent to those in the intact animal. Mammalian nenrea are usualiy mounted within a mall protective chamber which is suspended in or above a water bath, HAJi'f t^To.io Mo ro m tusrro In-meat of the preamt experiments, however, a fresh narvehad t be 4 mounted every 10 to 20 minutes and the temperature of even a small protective dumber could not be maintained by a water bath* Therefore a shelter, provided with a continuous and adjustable supply of warn and moist air, was constructed, --- The framework was made with Equipto Type 5700 hot dip galvanised ft slotted steel, l 1/2" x 3" x 0.104". The back wall which supports' I ( the warm air inlets was made of i/4" Teflon sheet, the other walls and the roof of 0.003" wyi*u sheeting. The horizontal dimensions of the shelter are 36" x 18"/ its height varies from 24 1/2" in front to 12 l/2" in back, the subsequent slope of the roof providing drainage for the water which condense/* on the incur aide* Within, a Mylar partition divide/?'the shelter into a 19 1/2" * 18" "outer" chamber and a 16 l/2" x 18" "inner" chamber. The former haj^ a permanent opening in front and jn used for mounting the nerve on the electrodes/ the latter /) tvUx shelter^ the nerve while its action potentials aper photographed. A thermistor probe suspended within 4 to 8 centimeters of the nerve and connected to a defleetion*type meter, Tale^ermometer Model 43, Type TF, permitted a direct reeding of the dry bulb temperature of the inner chamber whenever desired. .t DUP050044158 6 An myl9 supply of warm, moist air for the shelter was o. provided by an^lstw'Wftwfe'hefr constant temperature room} with the temperature of this row at 109.5F (1*3.06*0) dry bulb end lok,yw (1*0.28*0) wet bulb, 87$ relative humidity, the dry bulb temperature of the loner chaafoer was maintained at 37.06*0 O.V*C. IX. Serve Preparations: She left hind leg of the animal was obtained from the Pathology Section and the nerve removed: tibialis iron the dog and the sciatic with its tibialis branch from the rat. paring dissection the nerve was protected against drying by the application of a lactated Ringer's solution* ^(dognervea and the nerves fram the 18-manth treatment groi^ of -rate of the 2-year feeding study)"or by a `leilicone preparation! (360 medical fluid, supplied through the courtesy of the \ Insert UC^.. t'l safiufiW Dow Corning Corporationw* TheJRinger-'s - protcctedrn^ were suspended in warm Ringer^a solution for 1 yZ minutes before mounting while those coated with the ,mo* Jh --.* . elsercrode set within/the warm outer chj&Sber, The nerves were mounted so that the central end made contact with the stimulating electrodes, the peripheral mod (tibialis branch of rat nerves) with the recording electrodes. The rat nerves required 5 to 10 minutes, the larger A$ one dog nerves 10 to 15 minutes to adjust to the environment of the inner chamber^ * Cutter's for injection. f DUP050044159 7 A typical dual tracing*, copied from one obtained on a dog snra, is shown in figure ?. She sweep of the oscilloscope been Is from left to right) its speed 0,2 msec per division of the screen. The lower response was recorded by an electrode 2,48 cm distal to the stimulating electrodes, the upper by an electrode 2 centimeters farther along the nerve. The following discussion s applied to eithsr response. The first small upward deflection lasting 0.5 division (0.1 msec) is due to the stimulus current and is called the stimulus or shock artifact. Since this current is conducted by the nerve as by a wire end its arrival at the recording electrode is essentially instantaneous with its application to the nerve, it indicates the time of stimulation in the tracing. After a short delay, 0.?.y m *h e. <r,WW l,2 divielona-4Q*Sg.-aacj in the lower tracing and in :r ; *0 <SL-. the upper ^*. i^^4'vae^^inninff^of.the l'arge upward deflectionf*which ia the compound action potential. After Kissgaartir) $wo measurements were made: from the start of the stimulus artifact 1) to the beginning of the upstroke, the "Infliction", canned by the arrival of the most rapidly conducted impulses at the recording electrode and 2) to the point of maximum deflection, the 'fceak", due to the later arrival of the impulses of the largest group of similar fibers. These measurements provide the data for calculation of "inflection" velocity end of "peak" velocity, respectively. Inj thisjparticular photogrspji the T^TTTT grotwing thr nerve between aae ajttalnablej with :ffche ltplati|>n and re elec PJU O-SK*.^ 4 * Obtained with the Type 3A5 amplifier r~ttr "splits" the beam so that responses to a single stimulus can be recorded from two points along the nerve during a single sweep. DUP050044160 IV, Animals gtudledt 8 A total of 262 rat and 33 dog nerve* were teste^,^ She dog* were electro cuted! the 22b rate 0# the 2-year feeding study were ^chlorofowned. the other 'fW.. 38 rets maoprlsed w special high lewd dosage group hilledjr4tM^Hw^iftee.of aeaerTrettM^^ by decapitation in order to determine whither chloroform had a significant effect on conduction velocity, fable 1 gives the groupings of the animals according to lead dosage level and duration of treatment. k e s u i/t s , VAuofrf of fc&sefcvicfc cSMtfweTtPW .wctocrn'cs A If Solatlc-Tlblalla Nerves from Hats? Average conduction velocities with their1 standard deviations from the mein are given In Sable II. TU %. vwrtv? '(fay* I) rtf & W /1 ,A Herves from Decapitated Rats, , Inflection velooit4vthtr*-of"djh ' ...... Uteri t " 7UU~ festesb^fibers, aamcsgad &?^3 m/sec (meters per seoond }f-valuer which overlap those of 71 end 7l m/sec reported by Ellasson for nerves obtained from normal end starved decapitated rats (4), tits however, peah velocity, 'tha&r-of-tho ltupgaat-grcup of,,g,bdisri"f^ fd TO averaged bl fc> m/eec, diatinctly below his values of 53 # 55 m/aec* A p&Ci'ttfj. { ksXa-, S^ reason for this discrepancy is obseurebul) iusy,tntraBggglated'',wlth prgbliBfflMwmsed^^ / Fgin R*fS UVwc-o 01 cv\wwfh* 1, Jk jmcapltatioa versus" {Bflerofeawa, ^She nerves from the chloroformed rats of the l8*month treatment group bad higher,.those from the 2b*month / group lower, velocities than the nerves from the decapitated animals ^ien comparisons art limited to the values for equal conduction distances^ Although the average values do not support the expectation thavtim chloroform would depress conduction velocity, the large standard deviations Which characterise the measurements made on these DUP050044161 9 nerve* indicate that these preparations were not ae satisfactory as those obtained from the decapitated rats* However, age, rather than chloroform, could account for the variability*#or;the chloroformed animals were older than the decapitated and many showed gross evidence of degenerative Changes* re /XL* Tibialis Ferre* from Dogst She data obtained on all the dog nerves ere given la Sljble HI. Technical (oMWWScX **&> 4\ '*} **'&*y 4 Wt&sa. pvitou|*% difficulty with stimulation oeiaswi^ti^lBgirgaC the nerves finsta tthe four male controls* She avereges and standard deviations far each treatment group include cMvtsvaJS-* u mA- ^iUt. fw t*-L *t k4*~A (Vv^1 .tiv V**.., both sexes because of the small number of dogs par group end since a sea differ* A Win*. %^-v U KeA<A- V--V s" cA.f.^*, ace is not obvious. The conduction velocities* 84 - 102 m/sec for the fastest ,, i> . . - ' aawi a i. fibers and 46 * 58 m/sec for the Urge** grot^, are well within the range for mammalian fibers listed by Grumdfest (7), ,, ft Shfse dogs .were electrocuted, and relatively young) the standard devla* tions^eoapara favorably with those of the measurements made on the nerves from A the decapitated rats* H the affect of lead* Comparison of the conduction velocities of the nerves from the lead-fed animals with the values obtained for their respective controls does not reveal a- an .obvious decrease in velocity due to the lead* This conclusion is substan tiated by the results of ths F test for effect of treatment* which was applied to all of the data obtained at each sacrifice (Table IV). Although this test reveals a possible effect of lead on^inflection velocity of the dog nerves, * r jfm Varitoe* due to toil*mn% Variance within Group DUP050044162 0.01<p<0.05, the data of Table h i eve not convincing. DISCUSSION 10 The value* obtained fear inpulse conduction velocity in these experiments indicate that such measurement* are both practical and valid when made on the typ* of preparation available at autopsy with the possible exception of those from chloroformed^ animals^ The preparations from phlorofcanned)animals might be considered unsatis factory because of the differences in the average values obtained for the nerves from the 18- and 24-month treatment groups and because of the within group variability. However, the nerves from the 18-month group were protected with Dinger's solution during the dissections * the other nerves with the slUeone preparation?4'. When Dinger's solution is used idle humidity of the shelter environment must be very high to prevent drying of the nerve; the high humidity introduces recording difficulties which cause an apparent decrease in conduction time so that the calculated velocities are erroneously high (see below). The greater protection afforded by the silicone preparation Ats* permits the use of a lower humidity thereby reducing the error. ^ The reduced velocities of the nerves from the 24-month treatment group could be due to age; decreasing velocity with increasing age has beet reported for the nerves of rg DW4 ptirAww Bfi Tbs human subjects (5, 12, 13, 15)* The within group variations.might well result A from differences in the amount of fiber deterioration and in the amount of damage inflicted hy the separation of the nerves from the dense layers of fat in which they ware (diaracteristtcally embedded. Sim The use of the sllieone preparation began after the 18-month group sacrifice. j DUP050044163 11 For comparative purposes, technical difficulties which cause variable results can be mostly eliminated or controlled. A* The high humidity of the inner chamber causes a marked tendency for the action potential to move towards, and eventually fuse with, .AWtdWHt $ the stimulus artifact as the stimulator voltage ie-4npeesed--fcveTM- the maximum Tor tbs nerve. This apparent shortening of the internal between stimulation and response results in falsely high conduction velocities and the magnitude of the error (velocity increase) depends on the voltage used to stimulate the nerve. This error can be minimised by 1) using the silicone preparation so that a lower sy$Tf'4T)i'/ifs r#< P.noe ^ u j > *< ` a* humidity suffices, 2) sidmulating^bhe-a^ same stimulator dll Kirrttfy voltage which must be supramaximal for all, 3) wiping the electrode holder before mounting each nerve, and 4) using a long conduction distance. B, The effect of conduction distance per ee, obvious in the data of Table II, can be eliminated if this distance is standardized. Variables which, in these experiments, could not be shown to have affected conduction velocity significantly included 1) the dry bulb temperature of the Inner obentoer which had a maximum variation of 1.1*6 and 2) surprisingly, the time which elapsed, 19 to 47 minutes, between the death of the animal (chloroformed rats: from start of chloroform administration) and the placing of its nerve in the Inner (dumber. It is possible that the minimum delay between death and mounting, 19 minutes, is longer than some critical Interval altar which further delay has little additional effect. Theoretically, because excitation time is excluded, measurement of the time two it takes far Impulses to travel the distance between the recording electrodes rather than between stimulating and recording electrodes, should provide a more DUP050044164 12 exact determination of conduction velocity. However, measurements of the intervals between the inflections, or between the peaks, of the action potentials obtained from two recording electrodes during a single sweep t the oscilloscope bean (Fig. 3) provided velocity values which were so variable that this method of measurement has been abandoned temporarily. Since all of the nerves obtained during a sacrifice were treated as nearly alike as possible, comparison of the velocities of the nerves from the treated animals with tbs values of those of the controls killed during the same sacrifice, is valid. Such comparisons do not reveal any interference with impulse conduction which could be considered due to the lead. However, in comparison with nerves of other animal species, e.g. guinea pigs and rabbits, rat nerves have been observed to be resistant to -tbs toxic action of lead (5)j the nega tive results with the rat nerves in these experiments can probably be attributed to this resistance. No report on the effect of lead on the peripheral nerves of the dog has i tocmv been noted in the literature. Although at the time of autopsy, the three male fit 6 tebP % dogs lad hlood lead concentrations ranging from 91 to lit micrograms per 100 tos fa* . #t mm**. -- - * "**"* " >\ ^VMCS Gommlfr&btoM Uhidh *?* oaaidwad wdeairi&ly high, ibi dogs eppeared and ahowA m clinical sign* of peripheral nawc^&tfesr A.'Vv .IaA-1* DUP050044165 CQHCHBIGNS 13 1. Measurement of the impulse conduction velocities of excised nerves obtained from animals at the time of autopsy can provide a functional measurement of the damage inflicted upon peripheral nerve by a toxic compound. 2. inorganic lead, as lead acetate, administered to rats and dogs in the diet, in concentrations as high as 300 ppm for as long as two years and to rats In a concentration of 3000 ppm for ono year, had no significant effect on the conduction velocities of the sciatic*tlbialis or tibialis nerves* Report by: Mary E, Maxfield, Ph. D. Physiologist .^proved by: 0. J. Stopps, M.B. ,B.S. chief, Physiology Section MEM/dyb 12/11/69 DUP050044166 f Tfr5f trcmKt^o. <Lm. U V/\' fW f- TC'Sr t) poe e p f o -c t Gftoups TT -T7 c?1 + <? o f TfBt-ftTinf-nT IWFl. UG4-OC {K-M<- F = ff.*77 * (- ff "f* fw Cs - IJ*( .. riZe^ 5 -2. ('USV>VJ` doops T-B P- OMS' '- O' Hy pctt (o f c . 064-. " - J'-S' $ od\ I- " 4.#L I kjFC i i-H^( if ~1y ^ c ij ^ p - o.ri [v^l. trJl. IV$\0< iI o.oi <Z P <. o .t>.i' ^TGfT ftlTT-V, l-'tZ- IW ^ (|/ PL. ^tf <9. (ftp ` i- pec/, " f TST i Hi DATA I (WH. SmA^. HiUytv^o^' oP o.oi < P < o. or DUP050044150 lafpn ....... ... ,rami.,..............lMh ... Jweeh ........ .............. ,,.,,,..33,.$vl.fr1........... .... 5M.. `-iy(........ &/ *] ThT^.... -..: >...^.4... > 0:0f ^........................... fr.i ............... 0 01 > <? > 0, 0 r~ .............. .................... ........ . ,m I, M<ii|i jjmrrr -nT r^rv tf i~ T~y I v S ' W m's . r H* Cfc>-F $v.,... ( KS'16 V> .........^.r.. ................ / 'c '< n DUP050044151 Y\k Li 4 XT j Ji (s^y, j! (1D 4 U hdL &l' Y 2', S/JsIB 0- 5*i %x1 'T?~ iv} K D.r V V*1" 'V3 I0.97 tj$ (v V DUP050044152 Tlte pefi je veiocmes Fftch <so t o \ it r-- %!1 fa ^i*-<z/h~*-~A~ fa 6E ~ 3 ~ DUP050044153 EEIEKENCE8 14 1, Brturning, Ethel. ^icity of Industrial Metals. p. 157J London, Butterworblis, 2. and Johnson, E. % Motor Nerve Conduction Velocity in "Idlqpathlc" Polyneuritis. Archives of Physical Medicine and Rehabilitation 42: 159-165, 1961. ~~ 3* fiewaie, A. w. and Resell, D. J. Sensory Rerve Conduction in Patients with fiihetes Mellitus and Controls. Reurology U1 876.882, 1961. 4. Eliasson, s. G. Nerve Conduction Changes In Ea^erinental Diabetes. Journal of Clinical Investigation 4$; 2353-2358, 1964. 5. Fullerton, Pamela M. Chronic Peripheral Neuropathy produced by Lead Poisoning in Guinea Pigs. Journal of Neurcpathology & Experimental Reurology 2t 214--256, 1966, 6. Gilliatt, R, W. end Willisoh, R. G, Peripheral Serve Conduction in Diabetic Neuropathy. Journal of Neurosurgery & Peyehiatry 2Jk 11-18, 1962, 7. Orundfest, H. Bioelectric Potentials. Annual Reviews of Physiology 2 : 213-242, 1940, 8. Harvey, S. C, in Pharmacological Basie of Therapeutics. Edition 5} L. 8. God&ah and X dilman, editors. :Rew tork, MacMillan, 1965. Hutton, R. M. Lead Poisoning. Provincial Board of Health of Ontario, foaNalo^' c.w. Janes, 1923. 10. Kaesar, H. F. and Leabart, E. H. Nerve Function Studies in Experimental Electroaocephalogrephy end Clinical Neurophysiology, Supplement 22} Raw York, Elsevier, 1962. 11. Lambert, E. K. Diagnostic Value of Electrical Stimulation of Motor Nerves. Ibid, pages 9-16. 12. Lawrence, fi. G. and Locke, S. Motor Nerve Conduction Velocity in Diabetes. Archives of Neurology 485-489, 1961. DUP050044167 13. Mayer, R. F. Nerve Conduction Studies la Man, neurology |i 1021-1030, 1963. 15 14. McDonald^ W. I. The Effects of E^perlaentel Demyelination on Conduction In Peripheral Rem. A Histological end Electro- pbyafpblogleal study* II. Blectrapiysiological Observatioss* . ' Brain 86t 501-524, 1963* 15. Mulder, D. W., Lambert, E, H., Baatron, J, A. end Sp^rague, R. a. The Neuropathies Associated with Diabetes Mellitus. A Clinical and Electromyographic Study of 103 Deselected Diabetic Patients. Neurology rL: 275*284, 1961. 16. Sale, E. The Motor Nerve Conduction Velocity in Polyneuropathy due to Chronic Triorthoereayl Phosphate Poisoning. Electroencephalography and Clinic^al N2e9umr^opihys,io,logy, Supplement 22; New York, Elsevier, 1962. 17. Setae, T., Ferreyi, E. and D'Aaato, C. C. Velodta di Conduaione Nervosa nei Satumil. Folia Mediae 48 658-668, 1965. 10. Stepson, J. A. Conduction Velocity of Peripheral Nerves in Human Metabolic Disorders. * w* J6j *l 4, EiUctroencephalogrepby and Clinical Neurophysiology, Supplement 22; New York, Elsevier, 1962. 19. gkillman, T. G., Johnson, E. W,, Hfennd., G. J. and Drialsill, H. j. Motor Nerve Conduction Velocity in Diabetes Mellitus. Diabetes ID* 46*51, 1961, DUP050044168 FIGURES Figure 1 * Equipment used, in conduction velocity experiments. 1. Serve shelter. The air inlet to the "outer" chamber (see (o W<Vi<sL text) ie visible as a 'protrusion of the back vail. The A large electrode holder can be seme in the "inner" clumber. 2. Tele-Thermometer. J. Argonaut isolation Transformer. 4. oseilloscdpe mod Amplifier. 5. Tektronix Stimulation Unit. Figure 2 - large electrode holders connected to record from two points along a nerve, Si , 83 : stimulating electrodes. Conduction distance measured from S,, G : ground connection to nerve (any free recording electrode can serve as a ground connection}. R : recording electrodes. CR : recording electrode: common to both of the recording circuits. Figure 3 Copy of "dual" tracing obtained from dog tibialis nerve. SA : stimulus artifact. Measurements are made from the beginning of artifact. Ri : response from recording electrode 2.48 cm from stimulating electrode. % response from recording electrode 4.47 dm from stimulating , electrode. \ UitQV4< < \ I measurement of conduction time for inflection velocity \ (lower tracing). p measurement of conduction time fear peek velocity (lower Weeing). 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