"~rans~eBt in¢~eas:es ~B s:erum aspa~a~ e :~not . rans~erase (AS~ occur a~ te r in ltlat~:on of t o t a i pa~enterai n u t r i t i o n ~ N ) Zh~ ~nc=eas~: ~S cue ~0 f~ity ~trA~on, Of the liver. TO; fu=hhe~ Study ~he ~ag~Ors ~esponsil~ie for :the i~crease ~n ~T, we evaiua:ted all :adult pat fents Who received T~N a~ :£he Vamc0uver ~eneral l~osp~a~. C h a r t s Of 93 patsen~s were reviewed; chose pa t i en t s w l th c l i n i ca l or bi0ehemleai e~idence of ill, e= dysfunction prior t0 ~sta~t of TPN wet 9 excluded f=gm ~h e s~udy; ~is lef£ 519 patients in ~he study, A s~andard protocol was :fOllowed for TPN, The prdtein source was, a erysta~i~ne amiBo acid solution (Trav~so~). Cai0rles were suppl~ea as dex:trose and: Zntra. i~p~d. Vitamins i eiee~roly,tes and t~ace elements we~e adm~niS'~ered as ;required. Thlr~y~one of the 59 patients had an increase in ~ST ac£i:Vlty. In most cases the, peak AST was Seen 7~i0 days after s~artifig TPN~ An inverse dorrelati0n was obtained between the pea~/:basel~ne AST and the :Serum phosphate meesflred at the ~me Of ~he pea~ AST legal ( r = 0 . 6 9 , p. < 0,O~). Tens the h~ghest AST ~alu~s Were see~ in the @Orient% With se~zege hgp0phOsphatem~a (ph0sph~te < i.:0 mg/dL),~ Hypd~hosphatemia[ ~a~g~s deple£ioW of red Ceil 2,3 DRG Which ~eads tO hypoxia. Liver hgpe±ia Worsens ~h& ,degree Of fatty in ffitrati0fi in ~he il~er Whioh could accdunt f~r the increase ~n, AST,

411 C~REA6~I~E PROTEIN (CRP) ~N THE D~ONOSIS OF BACTE- R~ INFECTION ~N NEWBORNS. F~ Lari~r~ M. Mass0:~

J.C. ~0reat,: L±nd~ Nadeau, Jea~e P±Chet~:~ C. carrier. Set. v~ces de b±0chim±e at de ~onatei0gle~ hSpltal saih£-Fran~0±s

Severe bacterla~ Infee~ibn ~n pr~ture newborns carries a hlgh m0rLta~ii:ty race. S~gns and s~pt0Ms are 0lien subtle ahd unspeh~fi@. ~0 a~e±d u~edessa~y Use Of an£~b~0tlcs :in non infected neWb0rns it WOuld: be imp0r~afit tO rely on :a sen- sitive an~ s~edlfid hl0~og±hal merMer Of lhfection that Would: h~ ~read~ly available. We e~aluated the ~alue bf CRP as SuCh a marker. It was measured ~by an enz~e i~unoassay me ~ thud (~ZT~, s~). The ~eth0d w~s linear up to ~o mg/a~. T~e int~a~essay CV Was #.hZ and the ±n~er~assay ~V was 6.8Z. BlOOd Samples ~e~e drawn at the time Of heel PrlCkS for Other mendeto~ test~. ~RP was less than i mg/dl in all but O~e of the ~5 -babies WithoUt In,cot±oh. : The elevated result (.3.1 mg/dl,) was f0und in the firs~ 2~ h of llfe in one baby with sO#ere neonatal aSph~±a (Apgar l:). All four ±nfants with pro~e~ neonat~l badterlal !n~ect~on had results SUPer~0r ,tO

mg~/d%. Ser±al measurements in one with septicemla shewed t h e pi~entla! usa of CRP to mon~t~r the efficacy of the ~re~t~ mont. In 15 fnfan~ s with elln~cai 8usp~ei0~ of neonatal bac- teri~l ~ectlon, Who Were shown t~e be no n ±n~ected later, on~y two had results greater Lthan I rag/g% but less tha~ :3 mg/dL One was suffering ~r0m in utero foetal distress (re- sult a t i 4 h of ii~& :: ~.9mg/di)and the other hod a me~her~

of iife:: L3 mg/dl). :in C0ncius$on ~hese preliminary re- SUlts ~h ow ~ a ~ ¢"reaetive Prote~n may 5a a sensitive and spec±fic t e a t for the diagnosis neonatal :baeter~ai ~nfec- ~±ona:~ !:t ~Y> furthermore se rve ,to mon~t0r the a~f~eacy o f ~he t r e a ~ e n t ,

42 EVALUATION 0F T~ST~RETIN 'AS A B~O~HEMICAL MARKER OF PRo~E~N-~0KiC ~ATU~: OF P~TURE N~RNS.

Llnda Nadeau, J,CI. Forest, M, Masson, Fi Lar~ee, ~eanne ~ b ~ : C a r r i e r ' ~ e ~ e e s de 510chlmie at de n~o~at~d-

e~a~ua~e the :nutri~i0na$ :s~a~us Of premature neebOrns, We he, ve S~Ud~ed £ra~s~hy~et!~ in ~he eva~uati0n of ~he :pr0~eln-ca, i0~$C s~atUs d f 6he newborn and we ha~e :compared ~t:s :va'~ue ~0 albumln, tot~ pT0te±ns and anthTopome~ri~ ~ measures. ]~50 pre- ~ture newbo~s of 26 t6 36 weeks 6£ gestatT0n were divldea iA ;Ewe g:roups~ The "norma[ prem~tu#es ii ~r0dp W~ composed Of ,bah±~a Without ma~br patho~og&es in p~r 0S :feedlng Star~ tad W~thin t 0 day~ af~er'D~t£h, The sec0na :igr0ap ~aa c0mp0aed of:pr~res: W~th dempllca:£~ons delaying 0ral feed±ng. Trans÷ thy~e~n was measured bY radial ±~un0d~:ffUs±on. Within assay and inter assay C?tS Were Linearlty was: good up to 200 mg/L ~e~ght i0SS Was 114 g/day dur±ng the first week of life in the n0~: ErOU~ Whlle ~ :~aS 25 g/day : i n the secpnd group, The nO~,l gr0up had a~erwar~ a rapped Weight gain that rea- O~ed 20 a£ 4 weeks. ~he Seeond group had a Weight gain of I~ g/idey &t 6 weeks, Total :proteins and a~bum~n decreased S l~gh~ly In bo~h g=0upsi, ~Urlng the :flrSt weeks of l~fe: and : the=~r0ups d~d nO~ d~ffer: s~g~±f~cant~y from each Other. In t~he ~o~l group, t~ans:t~yret~n had a mean ~alue of 85 mg/i at two hours of l±fe and increased rapidly Up to ~ weeks tO teach

hours O f i:f-fe (mean : i36 rag/g) and de~reas=ed rap~diy to: 8~ mgl& a~ 3 Weeks of $i£e. ~ereafte= ~t SlOWlY ~n~reaaed: tO

130 mg/l at 9weeks. In eoncluslon, the changes in transthy- retin correlates well with the changes of weight of prematures and appears to be a good marker of the protein-calorle s~atus.

43 THE APPLICATION OF CENTRIFUGAL ANALYSIS TO TISSUE

~ HOLESTEROL DETERMINATION. Y. S. Huang, D. F. Horror±n. and S. Manku . Efamol Research Institute, Kentvilie, NS

Color±metric determination of cholesterol concentration in tissue is usually complicated and time-consuming. Cho (Clin. Chem. 29:166, 1983) has recently introduced a solvent system, dioxane-isopropanol (D-I, I:i) Which easily solubilizes the tissue lipid extracts into aqueous medium, so that enzymatic methods for determining serum cholesterol can be applied. We have adapted this system ~e automation using a centrifugal analyzer. Cholesterol reagent kits from different sources have also been evaluated. In our observatlons~ the color develop- men~ of free cholesterol standards (ranged from 0.25 ~o 5 E/L in D-I solvent) is complete within I0 minutes with all re- agents tested, but hydrolysis of standard cholesteryl escers remained incomplete even after 30 minute-incubation. This =esu!t suggests that the activity of cholesterol esterases but not that of cholesterol oxidase in the reagent was markedly affected by the presence of organic solvent, even though the volume ratio of reagent mixture to D-I solvent in this Study was set at 120:1. Severe interference was also observed when liver lipid extracts were analyzed for cholesterol content. These problems were corrected by saponifying the liver lipid extracts with alcoholic KOH and extracting the nonesterified cholesterol with hexane. The extracts were dried and red±s- solved in D-I sol~ant before being measured by Cobas Bio Centrifugal analyzer. With this procedure, the recovery of cholesterol reached 99%. Comparison of different reagent kits showed that the Boehringer-Mannheim kit give faster and better color development and this was subsequently used for all the analyses. Precision and reproducibility of automation was

4A A L ISP LANGUAGE APPROACH TO COMPUTERIZED

INTERPRETATION OF UABORATORY TESTS. M ichae l D.D. McNeely, Ken Gamble and E rnes t C .Y . Chang , L a b o r a t o r y f o r Compu te r E n h a n c e d C o g n i t i o n U n i v e r s i t y o f V i c t o r i a , and I s l a n d Med ica l L a b o r a t o r i e s , V i c t o r i a , B .C . C a n a d a .

A v e r s i o n of the a r t i f i c i a l i n t e l l i g e n c e ( A I } computer: l a n g u a g e L ISP ( F r a n z LISP, Opus 32) has been used to develop a model '!expert" system for the au.toma ted interpr~eta~tiom of I i v e r f u h c t i o n tes ts . A VAX- I 1/780 c o m p u t e r is e m p l o y e d . The p r o g r a m uses a k n o w l e d g e base of o v e r 200 " I F - T H E N " hu las w h i c h a re a p p l i e d to deve lop a p r i o r i z e d l i s t o f d i a g n o s t i c p o s s i b F l i t i e s . A sepa ra te ' set of r u l e s "s then i n v o k e d [o deter :mine the bes t t e s t i n g s t r a t e g y . The p r o g r a m has been d e m o n s t r a t e d s u c c e s s f u l l y w i t h 100 cases d e r i v e d f r o m hoso,i:t a.I r e c o r d s and [he med i ca l l i t e r a t u r e . F e a t u r e s d e v e l o p e d f o r t h i s i m p l e m e n t a t i o n i n c l u d e ; ( I ) a " u s e r - f r i e n d l y s h e l l " !o permi ; t an e x p e r t to a d d and modiTy r u l e s , and (2~) the p r o g r a m ' s ab i i t y to i revea l the og c used n arriving a.t a conclusion. We feel tha t a p p r o a c h e s

such as th i s may u l t i m a t e l y be used by p h y s i c i a n s on a rout : ine b a s i s d u r i n g the ' n v e s t i g a t i o n of d i f f i c u l t cases end f o r o u t l i n i n g g e n e r a l d i e g n Q s t i c s t r a t e g i e s .

45 LIMITATIONS OF HAIR ARSENI~C LEVELS D. Robinson., R.F. McCurdy and J.T. Hirdmarsh, DFvi:sion of Olinical Chemistry, Department of Pathb'logy, Dalhousie University and Victof'ia:General Hospital, Halifax, Nova Scotia, B3H IV8 arid OttaWa Civic Hospital, Ot:tawa

Arsehic contamination Of groundwater in Nova Scotia was firs.t identified in Febr0ary, 1976, when a resident of WaVerl;ey was diagnosed as be%ng a victim o7 arsenic intox- ication. The patient in questi~on had a hair l,eve] of arsenic of 40 ug/gram •, with an upper normal limit of approx- imateI'y I :ppm. The patient was supplied With bOttLed drinking water a~d after a year his ha;.i r arsen:i~¢ ]level dropped tO I~2 ug/grani, still Considerably above the aormal range. The pail,an,t, at thJs time, was •using hks contamin- ated water folr bathing.

Laboratory experiments, were designed to determine the rocation i-n hair of exterra,lly applied arsenic and arsenqc entering the hair from the subject ingesti'ng Ft and I:o see i:f these two types can be dfs.tinguished.

The ~esults of these expe:rimen:ts p'lus subsequent hair levels from the patient after £.omp!:etely abandoning his contami:nated water source will be presented. The role of

206 CUNICAL BIOCHEMISTRY, VOLUME 17, JUNE 1984

endogenous and exogenous sources o f arsenic and t h e i r c o n t r i b u t i o n to ha i r arsenic leve ls w:i ] l become obv:ous

h6 HAIR AS AN INDEX.OF CHROMIUM STATUS AND IMPAIRED GLUCOSE METABOLISM

G. Dowe and R. McCurdy, D iv i s ion o f C l i n l ca l Chemist ry , Department of Pathology, Dalhousle University and V i c t o r i a General HosFital, Halifax, Nova Scotia, B3H ]vB

The potential merits and ] imitations Of ha.ir analyses as an index of chromlum Status wi l l be reviewed in l ight o f the relat ive inadequacy of more tradit lonal biopsy materials. The need far such an index IS further Substantiated by evi- dence indicating that sUboDtimal chromium sutr i ture may exist in the North Amerclan population with a concomitant incidence of glucose into!lerance associated with decreased levels of glucose tolerance factor (GTF). D i f f icu l t les associated with meaningful interpretation ofldata w.i11 be contrasted wi:th the correlatlon of haif chromium to an indlvidua1's known chromium status. The Feasibi l i ty of this technieue as a screening test for diabetes melIltus wi11 be examined.

47 NEPHROTOXIC EFFECTS OF URANIUM N DR NK NG WATER AS DETECTED BY

URINARY PROTEIN ELECTRoPHbRESIS

D.C. Campbell, C. Oymond, M.A. Moss, R.F. McCurdy Dept. of C n cal Chem stry, Dalhous e University, Hal' faxl N.S , BdH 4H7

The purpose of the s~udy was to detect early nephro- toxic e~fects of uranium i.n the drinking water of adult rats. Male Sprague-Dawley rats (8-10 weeks) were Fed uranium, 20 mg per kg body we;ight per day, via gas.tric intubation daily. Twenty-four hour urine specimens were collected over a ~wo week per od and each was concentrated f i f t y times using Minlcon B-15 concentrators. Electro- phoretic separation of the concen,trate was :carried out using an agarose gel system. The ef fects, produced by uranium, were manifest by proteinur iawith in as short a ~ime period as one day. Proteinuria was: not only seen as 'ncreased amounts of Albumin but also, and more signi f icant ly, as an increase in globular protein, especia]]y in the Beta region of the eIectFophoretic pattern..

~8 INTERLABORATORY STUDIES IN CLINICAL CHEMISTRY IN CANADA - SUI~Y HIGHLIGHTS OVER A TEN-YEARPERIOD

M. W. Weatherburn, Bureau Of Medical Biochemistry, Laboratory Centre for Disease Control, Health and Welfare Canada, Ottawa, KIA OL2

Target values for accuracy have-been assigned by means of CSCC - approved reference methods to haman ~erum samples in nine inter~aboratory studies. Constituents, usually five per study, have included calcium, magnesiam, creatinlne, glucose, sodium, potassium, urate, total protein and cholesterol. Interlaboratory accuracy and precision have been calculated on eachspecimen; intralaboratory accuracy on all specimens within each study. Methods, or method/ instrument systems, have been ranked relative to each other for these three categories of accuracy and precision.

Some instraments ranked very well for ear.rain constituen£& yet poorly for others. A number of methods gave accurate results with serum but not with lYophilized materials. Some general Observations common to all constituents are: (i) benefits can be derived from £1ght limits of daily quality control, (2) improved inter laboratory precision can follow from participation in regional quality control programs, (3) potential problems exist in the interpretation of analytical results due ~o (a) wide range of laboratory reference ranges yet no difference in analytical results or (b) differences in analytical results when laboratory reference ranges were similar.

h9 DISCRIMINATION BETWEEN OBESE HYPERTENSIVE AND NON- OBESE HYPERTENSIVE PATIENTS ON THE BAS~S OF SERUM LEVE5 OF "PSHUDOCHOLINESTERASE, (PChE).

V, M. Prabhakara~, V. ~helan and K. H. Kutty, The Laboratoriesof the General HOspital and Janeway Child Heal:h Centre and Memorial University of Newfoundland, St. John's, Newfoundland, Canada.

A large percentage of obese and hypertensive patients have increased serum PChE activity. The objective of this study was to ascertain if any discrimination can be

made. between hypar~ens~yeS Wl~h and Wi~hgu~ ObeSity On the basis of Serum PINE, and l~pidS. Prel~minary c~se studz o~ I0 patients with h~ertensi0n iS presented,

In non-0hese h~erl tensiVe~'~5~,serum ~I~ChE; showed @ante Of 2283~36~6 ~O/:L {mean 5005 Z 11 SEMi, , " ~ri~iyeerideS a range Of 75:-= l:Sl mE%; (~iS +- 2 ~44) and che~eStez01 ca rang e o f t72 - 2~3 mg~ (205 -+ 2.45) , By' contrast, ~n dbes:e h~ertef is£ve~s.~se~ PChHh~s a range e£ 3550~6777 IU/L (mean 5232 - 15 .2 S£24), • r igl) ,eer&des ~ r a n g e 0f:i[35 - 120S rag% (476 • 9 , 2 ) a n d chd~esterol a. range of 252 - 500 mg~ (273 +~3.19. Normal range on eu~ methods: f o r pChE i s 2400 ~ 3400 IU/L, tr~glycerides 74 - 177 mg~ and Cholesterol 150 - 250 mg~.

Ne ~he~efore p r o ~ s e t h a t serum P~E:has a good diserim2natiue, value in ldentify~ng n0n~obese, ner~- l~pemic ~ypertensives from obese,, h~erl~pemic h~ertensives.

510: URINARY: PRO~FEINS iN' BREAST C~NCER C.L. Cousins and S.D~ Rice, Department :of Pathology; Div;~ o f c ii:nic@l Chemi.stry, Vic~oF!a ~enePa:i'Hosp]tai, Halifax, Nova Scot.is, B3H iV8

C0ncentra~ed humar urinary p..ro~eins fr0mPati.ents w!~h breast cancer and a control grouP were sep@,rated by using high reso]utlon two-d!mensionaI e ect r0phores i :s : The ~esuIts of th is preIiminar Y :study show basic s imi lar i t ies in a:]] patients sinre thece a:~e f lve charaCterlstic land- markS in the e]ectropho~etlC patterps. However, in six out of the e]even cancer patients here is a l'i:ne of Unresol.ved protein/s that travels jus~ below and to the r ight 6f ~1 - acld glycoprotein which is not present in the. seven patients o f the control group. This dlf~erence may be asS0ciat~d with the ~umor and its appearance may be :dependent on the type, stage and grade of the tumor. This protelh or pr0 te ins may have c l in i :ca l s i g n i f i c a n c e as a pb ten t i :a l mark" er protein for breast cancer.

51 EARLY TUBULAR LESIONS I:N :RAT KDNEYS AFTER URANIUM EXPOSURE

K.E, Keller, A. T r i l l o , M.A, Mess, R.F. MeOutdy~ D.C. campbell:, Department of Pathology, DBIhousI:e university Halifax, NOVb ;SdOtia and V:ictoria General Hospltal, :Halifax Nova Sc0tcia, B3H IV8

Thi:s is a report Of changes seen by l],ght and e!ecfron microscopy in ra t k idneys a f t e r uranium i :nj :ury. During preliminary Studies. a group of male Spragu e Dawley rats were dosed W;i'th u~anYI nltra:te so]utlon vla gastrlC tube, over a tWO week period.

The morpho :og cal changes during th e injury and recovery phase have been co'rrela~ed with p01yur-la and pKoteinuria occurring in these anima.l:s

Our Sl;Udy is part o f an investiga:tion ~o estabiish the tOXiC ef fec ts o:f uranium in d:rl.nking water., correlating morPhologlca'! and::chemlca! indicators pf injury and pre- y:in:log toxicological data relevant tO human drinking water gu:ideiines for uranium.,

EXPERIMENTAL PATHOLOGY POSTERS

52: THE:ROLE OF PMNs. IN THE PATHOGENESIS OF SlLICOTiG FIBROSIS.

D.H, .Bowden and I,Y.R. Ad~son, .Dept. Of Pathology, U~vers~gy Of Man±toba, Winnipeg, ManitOba R3E OW3

Silicosls iS usually: attributed to flb~oblas t st]mOlar]on by secret]otis Of damaged alveolar maerophag~s (AMg, The role of FMNS and elf continuing dell ~njo~ in the pathogenes~s now studled. MiCe, injec:ted in~ra~racheally ~th 2~ SiO2~ reCelv~ ed 3H thymldifie I hour before death at intervals tO 20 weeks. cellular populatiOnS and lySosomal content of lavage fluidS: were correlated ~th: morphology, DNA Synthesis and COllagen C0ntent of tNe Iong. The Iniglal response invo1~ed rapid PMN and AM recruitment ~0 ~he alveoll. Foea~ Type. 1 cell damage was rapld~y repaired by Type 2 tell pr011fe~a~i0n. ~l:though PMN and numbers dropped' after a ~ew days, ~h~y n~er reached Control [evils and rbse again after 8 weeks. Disrupt ~ 1onof bdeh PMNs and AMS w~th Silica WaS observe d in legated Cell pellets<. G[uCosamin~dase and glucur0[nidaS~ levels were ~ a~ways h~gher than ~ontr01s thr0ugh0u= ~he s~udy. Labe1~ng Studies :shOwed contlnui~g ~le~ted :D~ synthes&S by: in~er~ Stit~al cells tO 20 weeks; Increased c0[~age n synthesl s was found from 4 weeks onward, some free Pa~C~e~aS ~rossgd TM~g i epithelia! cells: an d a few: silica ~art~cles were fqund interstitial macr.ophages, The res~s ~ ind±ca~e ~hat ~e0ntlnu~n8 injury £0 and ~s in al~eeil and ~n the ~th

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