c· ·ctex.),... · la?)oratorie::; and several general service rooms anc1 offices. the...

10
: 2·1·8 · 1'21 12/1975 ? rof e-;:::o:r: ,. ':Jhyte, B.S c., :'.3 . f: . (Ql d .), D.P'lil. (Oxon), r.n .c. P., P rofesnori a l :7e llm1s ? • J. ..l e o te 1, : '.• D °' r, ·::::. . , C!.1 . :1. (Cane , !!'.:1.C. ? ., ":! •.• ( S7d .), P . · . • A.C .P. ; ., •. "'... DenJoroug1, D 0 P: ·l il. (O::on) , 'I 0 D. (" el:-, .) , .S enior .:\rd lie, P ootr octoral J.V. T rlO\'<l , ''. . D ., · ( '\del.), Ph.D. v ··o· - ..... " " ,.. r ) , M ..... ·r lC'!O ,., ... . .. n a, ' • .e .• -=> C. _ ,el.O . - •. j. e n, u ot.>• !' 0 !. D. (fro .. ' H onorary Vi :: ;.i tin g Fe llo•1s (until July) ; · cTex.), .3 . ,. ( 8asJ:. ) (w1til C.Jane :!e.r d, ·· . ,'.\.. . (Oxo11), Ph.!1. ( 3ir:.1. ) • :: 1onorary ·1ahl qvist, H •. '.a •1 .Sc. (AO.el. ), ·:.n. (U:;:>psala), .n. ( Ade l). : Ionorary :..,esaarc .. 1 · 3 . G. rJ ilmsh u rs t, ·:.D., 3.S. (Burroughs . . in Clinical " 'll armacologyl (until Sep temher) !atl1alie :r.. ... 1 r: c. (Gy ·" .) Cert. ox D ietetic!> / . 7Ul d rea B . ? o yl'.'!er , •: c. C!a tion nl : re a rt i Rosemary L. Ryall, . B.Sc., K.L. .B.Sc. (from rtarch) .. . : tea d 'fechnician P ryke, 1' .. . F. A.C.D .S.

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2·1·8 · 1'21 12/1975

? rofe-;:::o:r: ~ ,.

:r . -~ . ':Jhyte, B.Sc., ·~.~3., :'.3 . f: . (Ql d .), D.P'lil. (Oxon), r .n.c.P., ~ . ~ .~ .c. ? .

Profesnori a l :7ellm1s ~

? • J. ..le o te 1, : ' .• D °' = ~ • r, • ·::::. . , C!.1 . :1. (Cane ·-~'o'.lm) , !!'.:1.C. ? ., ":! •.• 2~.r:: . ? •

( S7d .), P . · . • A.C .P. ; ., •. "'... DenJoroug1, D 0 P:·lil. (O::on) , ' I 0 D. (" el:-, .) ,

.Senior ~ ollou ~

.:\rdlie,

Pootr octoral ~ellmTS ~

J.V. TrlO\'<l , ''. . D.,· -3~S . ( '\del.), Ph.D. (" J.c'~ .) v ··o· ~" - ..... " " ,.. c· r • ) , M ..... ·r lC'!O ,., ~ ... . -~ .. na, ' • .e c· .• -=> C. _,el.O . - • . j. ~ e ~ n, u ot.>•

!'0

! . D. (O~:: la .) (fro .. -'.UCJU~ t) •

' Honorary Vi ::;.i ting Fe llo•1s ~

(until July) ; ·cTex.), -~ . s .,

.3 . ·~u-~c~10<1h:ir , ~J .Sc. (;10~·1 .) , . :.~ . Sc. (~unj.), ·: . ~;c. , P'1. D ~ ( 8asJ:. ) (w1til July) ~ C.Jane :!e.r d, ·· . ,'.\.. . (Oxo11), Ph.!1. (3ir:.1. ) •

::1onorary :?a llou~

-~ .L. · 1ahl qvist, H •. '.a •1 .Sc. (AO.el. ), ·:.n . (U:;:>psala), :· .n. (Adel).

:Ionorary :..,esaarc .. 1 J?ellow ~ ·

3 . G. rJilmshurst, · :. D., 3 . S . ( l'.c~el.), !3'.~. ~ .C. !,, . (Burroughs . . ·.J~ llcone ~ellm1 in Clinical "'llarmacologyl (until Se p temher) •

!atl1alie :r..... ~Iavenotcin 1 ~1 . r: c. (Gy·" .) Cert. ox Dietetic!> / .7Uldrea B. ? oyl'.'!er , ~J . •:c. C!a tionnl : re a rt ~?0Wlc:':1tion) i Rosemary L. Ryall, .B.Sc., ~h.D.; K.L. ~ustin, .B.Sc. (from rtarch). . .

: tead 'fechnician ~

··~ . G. Pryke, ).1'.I . ~: .L.?., 1' .. . 1\ .I. ·~ . ~~· ., F . A.C.D . S .

2. 12/1975

' "'.°'(' · ·~\ ' '\("'. T - .... . •t ) &_ J.• - .. ~ •

In troc:uction

Th is ·J~ :Jart1 .ent. is loc;~ted ~everal :mndred yards from the John Curtin School in the ('an·x~rl:'a !Ios9ital, u'1ic'.1 ;1as a:Jout GO ~)edc. '..'.'h-=> Department j!as accomnodation for 12~16 in .. :_1atients, facilities for dealing wi t ;1 arn.bulatory patients, five !.1ain la?)oratorie::; and several general service rooms anc1 offices.

The :Iospital~'Jased section of the De~?artment accer>ts clinical responsibility for the inw~stigation an~. treatment of patients and }.'.>Ursues a ~) rO<:Jramme of clinical and l;:uoratory research oriented generally towards problems a::;sociatcd ·.Ji t!1 coronary heart disease and rnuscle metabolis"n. Studie r. embrace t he inv~ctigation of lipid 1 car~1ohydrate ancl endocrine Met~>olisrt\, hypertension and thronlJus formation in relation to o: Je <Ji···y, diet and other factors ~rhich are incriminated in a susceptibility to coronar.{ dinease, and studie£; on muscle cell ne1,t:;ranes o Studieo are being carried out in patients •:Ii th hyperlipidaemia v din~ 'etes u o}:>esi ty, hyper·, tension., ru"ld malignant hyper1,Jy:i:e:::ia as t!ell as in normal subjects. E}..::>eri~nents are also '.Jeing conducted in anirlals . ·,ror1..: done in Can>erra !1as been linke<1 uit::\ ~-!ork in i.1eu Guinea were the prevalancc o :~ coronary d~.,;sea-;s is r.1uch less and t1iet., rneta~...,olic ancl. other characteristics s o very d ifferent. Colla~Jorative worl:. hn.s also ':ieen 0.one •. r.i t.h uni ta of t'1e Commonwealth Ccientific and Inc.1uotrial :1esearch Organization in Sydney anft elnewh~r.:! o

•.rhe · '.edical :~.e<::ristr"'!.r, t :le i!nsident '.:e <..~ical Officers and t he '.:G~earch :": is tr;rs arc :::rovi1~.-c1 :)y t i1e hos:>ital. :aster Go ·· 1arrcn ~raG in c· :arg~ of t :1e •·rard.

C!"olasterol meta:.,olism (i ieatel o Potter, :'~udc:1oa\:a::c, norn:Na p

:.:avenstain)

1. Dietary stu-!ies ~·.rit~1 polyunsaturato(,. rur~inant fats ~Jere cxtencled to stud::_r the interaction of fatty n.ci0.n uith d ietary c~1olesterol ~ sterol e~{cretio:n was greater <tJ:1en a l ig~1 cholesterol inta!-:c -:-ras eaten ui t~ 1 !>Olyunr;aturotec than u3. th rnore saturated :Eato.

2 . i::i:1~ uzefulneo::; of volyunsaturatec1 pork in lmmring plasma li:'.lido uac Gtudied '>eca·.lse t :"e c iatrL\ution o:.: fatt:! acic:s in the glyce~ir1e ~:tol~cule of ~ig m~~at is J.i:C:~erent fror:.1 t~. 1a -:.: in ;?lant a'1d ot:ier ri. ~1.irnal fat ::; . i::Yevert!1eleµs , in comne.rison t;Ji th conventional porl:., ::;olyuns :i turatet:i. ? Ort in t~1e cliet lm·rered plasma cholesterol and increased the excretion of cholesterol by amounts that exceeded the reduction in the plasma pool.

3. Dietary cholesterol may raise the serum cholesterol less uhen the fat intake is low than when it is high. Stu<lies to date show that a low fat, high cholesterol diet leads to little change in the serum cholesterol because cholesterol synthesis is suppressed by the w~ount that is absorbed.

4 • . Studies in young infants have shown that the serum cholesterol level is lowered by polyunsaturated artificial milk or breast miU~ from mothers on a diet rich in polyunsaturated fatty acids. As in adults, the excretion of sterols is enhanced.

... . ..

12/1975

5. The bile acid, chenodeoxycholic acid, was found to . . loweX'.: t.l].~ -. ?erum .triglyceride and cholesterol levels :i..n hyp~r~ lipida~m,ic ,subjects. One possible mechanism of action w~s shmm t<:> !;>e suppression of sterol synthesis. · ···

6. Ethanol-induced hyperlipidaemia and carbohydrate""; . induced hyperlipidaerr~a were found to be separate entitieo.

7. The hyperlipidaemia of pregnancy was studied in a large number of women in considerable detail. Chari.ges in lipoprotein cholesterol and triglyceride were related to changes in the production rates of cholesterol and bile acid.

g 0 'l'he value of measuring the cholesterol concentration in ·wnbilical cord blood ~-:as evaluated in 200 children retested at one to 2 years of age. ri'hc yield of familial hypercholester­

. olaemia was found to be less than l~ but it led to the discovery of other. afflicted mernbero in the family.

9. A new rapid method has been developed for measuring th~ synthesis of cholesterol in man. The rate of conversion of squalene . to pJ.asma cholesterol me ·'isured during. infusions of radiomevalonate gave values comparable with those obtained. by the much longer sterol balance technique. · ·

Cholesterol metabolism in Hew Guinea.~s (tJhyte, Nestel)

Further studies carried out in conjunction with the Papua Hew Guinea I .nsti tute for :~1edical Research showed' that the feeding of cholesterol supplements (as egg yolk) suppressed ~yntllesis . without disturbing the overall metabolic flux of cholesterol or plasma cholesterol concentration. The ·subjects were eating their traditional diet which is practically qevoid of fat and cholesterol and very rich in carbohydrate.

'i.. -

1. :lole of lipases in huma"n lipo:QFotein interconversi,ons (!leardon, Fidge, ~Je stel)

Studies in vitro have clear-ly demonstrated the formation of lou density lipoprotein (LDL) from very low density lipo­protein (VLDL) at a rate ,_,,hich :i:.s dependant on the arnoWlt of lipases in h •JE.an . r.-1::-~mr~::t· d;knroral different plasma lipases, of different origins, are being studied. vJhen lipoprotein lipa~e of adipose tissue origin was inhibited by the addition of O .1 £:1 HaCl to the incubation system the formation of LDL was markedly reduced •

. . 2. In vivo turnover studies o.!_ human plasma very low . ·density . and low density lipopro~ein (Fidge, l'·~estel~ · Reardon) · · · ··

... ·. '"' /....; - ;

,· 'l'he . purposes of these studies are to determine .i,f all plasma LD~ is derived from VLDL, at what rate it .is sypthesised and how much of the total VLOr.. secreted into the plasraa is · transformed into LDLo VLDL, . isolated fr.cm normal ·volunteers, is iodinated and injected hack · into the same donors;., · ~ipoprotein

. . : .... ; .

4. 12/1975 "!_\~ \~-

-.5 ,·.Ji . .. :- . -. . "'

.. c;:lGlp,se,~ C;lre ,.s1:11Js..equently separated by ultracentrifugatl:on . · !;:<?~ :;;er..~~J ~ampl~.s 0£ ~)lood and the apo~B proteir,·, common to l>oth VLDL and __ LDL, is isolated f rorn both lip'oproteiri's · and the specific activities aetermined. Present indications are that all· LDL is derived from VLDL, and that ·an ·intermediate­dcns~:fy:, ~i~~pro:tei.n, . LDL1 , is a more imt\ediate precursor1J0f- LDL than the larger VLDL molecules. 'l'he fractional cataholic rate and tun1ov:er rate of LDL has · been calculated from kin~tic analysis. of . the .va~ious moieties.. This rnode 1 may proy~ .us:e .ful in e:>..rplai,ning abnonuali ties observed in several well documented hyperlipop~oteinaemias ..

3. CompaJ::'.ative .studies on the structure of a;_)o.li~oproteins Cfid.g~, Poulis)

VLDL 'and HDL apoproteir.~ . ha"Te been purified by ge(~an~ ion exchange chromatography from humdn, pig and rat sera. ' The peptides were then characterised by polyacrylaraide gel , electro­phoresis 1c· an.dmo. acid analysis and c-terminal residue identific­ation. Results have sh~m 1-.1any similarities between 'tliie smaller m.ol.ecu;tar wei9~t peptides of hu.-nan ar..d rat, suggesting '#.e presence qf . ho}-q~logous peptides in these two species. ·However, since porcine VLDL, unlike t.Yiose of humans and rats, has 'only one major small peptide and does not possess cofactor ~ctivity against lipop~otein li.pase, its :!:'ole in VLDL rletabol~rn is being investigated.

'• ,. J '

4;~ L.ipoprotein metabolism in the rat (Poulis,"· J.ilidge)

A ·. ~tho~i pas · been developed for determining the · s1:)~ci~;c .. ac:tiviUe~ of the apo-B protein pre~{ent in hqth VLDL and ·tDL ,. cmd of the ·sma,ll molecular weigi.1t c peptides coinrnoh to· 'vtni;,' . ·~ ;~ • \ t ~ I '- • •. • , • ( l-

and HDL. , It. has been possible to demonstrate that a·11 'plast!.la LDL is formed from VLDL but only 12~ of VLDL is converted to LDL, the rest presumably being rc.r.-:i.dly cataboliscd .:.n the extravascular compartment... ·'1'he data also suggests that some, b~tdlP~~ al,l, of t~1e C pe9tides are transferred · ftom VLDL to LDI:.- "and'~HDL •.

' ,·,, ' ... • • t '

Adipose tissue_metaboli.~m·

:,.,) 'i;, -Li ··ol sis and ester:i fication in human adi ose tissue. ~ ., .,r.;;. · Goldrick, Chinayong

.. ! , .•

, : ." Stucii~s are ·in progre s ·;; to examine the effects of diet on lipoly~~s. of· triglycerides and esterif ication of free fatty . acids in vitro in biopsy samples of human adipose tissue. A second objective is to detenuine uhether th0 ability of . adipose tissqe to . take u.p or .. release free fatty a.cids in '.Yi.t;r:o during die1;:·~cy .. ~ 6.-&1ges bea:r;$ ·any relationship to the development of hypertriglyceridaemia. The isocaloric substitution of carbohydrate for fat in t.he diet has produced 7ariable elevations of the plasma triglycerides and a diverse pattern of responses in adipose ti~sue from .the different subject3 studied ~o fdr~ .- The rates of lipolysis and esterification in adip·ose tissue _appear unrelated . to -the concentrations of plasma · triglycerides·· ·eH~her before or during high carbohydrate feeding. :Ji th starvation the rate of lipolysis has increaseu ani.1 esterification has decreased.

s. 12/1975

2 .• Glycerokinase in human adipose tissue (nyall, ·coldrick)

Glycerokinase has been found in human adipose tissue and is being characteri:::;ed. · It is similar to the corresponding enzyme in rat adipose tissue in that it is present in the soluble fraction of the ·fat cell, it has a · pII optimum ·o·f )}.6 and it is partially inhibited by iodoacetamideo The activity of glycerokinase is much lower in huntan than in rat adipose tissue·, a finding t·1hich is consistent wit1'1. the relativ~ly low rate of meta.nolism of human adipose tissue~-

3 •·. Postnatal devclo rnent of rat adi "Ose tissue metabolism (t1ard, Goldric!t

The development of lipogenesis in adipose tiasue and its stirnulation by insulin have been exat11ined during the postnatal development in the rat. Fatty acid synthesis in vit'ro . increases at weaning in epididymal fat but is not stimulated by insulin in animals younger than 25 days 7ost parturn. Progeny from mothers on a low protein diet 6% protein) during pregnancy show lower rates of in vitro fatty acid synthesis. These animals shou a sirnilar response with insulin to that in control ·anima_ls when glucose. is used as a substrate but show no response when acetate is used as a substrate. ::teasurement of enzyme activities demonstrated no significant differences between protein-deficient and control animals for acetyl CoA

· ·carboxylase, fatty · acid synthetase and citrate cleavage . enzyme. However, the protein deficient young had abnormally row activities of roalic enzyme at all ages studied and shmied some reduction in malate dehydrog~nase. . ;~ ,

1;,

At present a tlefective malate-pyruvate shuttle would explain the depressed ratcz of fatty acid synthesis observed and this is supported by the enzyme studies. The role of gro~rth hormone, which is reported to be reduced in this condition, will be studied in relation to the · development of ~atty acid synthesis.

Platelet function (Ardlie, Akbar, Nestel) .

· 1. Platelet function is being studied ·in individuals .. 11~ith various types of hyperlipidaemiao 'l'he synthesis o.f ' · ·

"cholesterol and other lipids is being measured in platelets and differences attributable to disease states and drugs are being studied. Incubation of clofibrate at therapeutic · concentrations with normal platelet in vitro decreased · aggregation and release by ADP, .epinephrine and collagen. In subjects with hyperlipidaemia clofibrate prolonged the bleeding time and inhibited the platelet release reaction even when the drug had ·little effect on plas1:la lipids·.

6. 12/1975

2. Studies of the influence of ~ietary cholesterol on p~atelet, funstio~ in rabbits .:lre continuing. _ : Th.;i:~S.- _experimental

· oys.tem is beinq- --used to explore the possible role of platelets in .t;he inqeption,, of· ·atherosclerosis. ... -,

,,·:

· 3 . ." Catecholalnines in the circulation may provide a "link between tjlrombosis and the smoking habit or behavioural · : · patteJ;'n of ·an individual. A plasma catecholamine assay i ·s · being developed and t:ie relationship between plasma: catecholamines and platelet function is under investigation.

'~ . The study of disorders of haemostasis is providing valuable information on the nature of haemootasis and the mechanisms involved in this physiological response. Investigations of hereditary thrombocytopathy has sho~m the

. . dependance .of platelet reactions on platelet coagulant · act;i~i.ty. tn individuals tli th von ~7illebrand us disease,

·· rece·n~ )-~t1~die.s have sl1o~:m ti1at tl1e von tJillebrand facto'r · · may be ·,:;involved in the platelet release reaction. .. ... · .. · .. .

"· · ' lius-i::"le. metabolism (Denborough, i-Ielson, Austin) I '

1. Identff.ication of susceptibility to malignant h:q>e.-r-pyrexia ...

A specific in vitro muscle test has been developed t.o identify susceptiQility to malignant hyperpyrexia, ~ dangerous and often fai;:ai: complication of general anesthesia in" tnari. This follmis earlier wor!c which established that susceptible inaividuals are' all suffering from an inherited disease of ' muscle, which is usually oubclinical, and demonstrable only by biochemical evidence of raised muscle enzyme levels in the serum.· . . .

. : ~. Studies on the bioche.i-nical basis of malignant _ ·11yperpyre,~ia

· The availability of a breed of Landrace pigs susceptible to malignant hyperpyrexia has pro~vided an animal model to study the biochemical basis of malignant hyperpyrexiao In vitro muscle experiments on these animals and on susceptible humans suggest that all ti1e clinical manifestations of malignant hyperpyre::da result from a raised .calcium ion concentration in in the .:.nyoplasn in rP.sponoe to general anaesthesia. The exi;)erir.lentl'.l system provides a unique approach for exploring' the role of calcium ions in biochemical reactions in muscle. ·

3. Treatment of malignant hy·perpyrexia ·c

Studies of the effect of local anaesthetics I and other-'· drugs which control calcium movements .'.in muscle cells, on the abnormal responses in nuscle in malignant hyperpyrexia are being done in man and in susceptible pigs in the hope of developing an effective treatment for malignant hyperpyrexia.

. , 7 • 12/1975

4 . I nsulin secretion in malignant hyperpyreJ=ia

The analogy between t he role of calcium in excitation­contraction coupling in muocle and its role in the secretion of insulin, led to an observation that glucose ·-·induced insulin release is increased in individuals uith the muscle disease predisposin·g to malignant l yperpy~·exia. ~his implies that the rnembrane abnormality uhich is present in the muscle cell in this syndrome is also present -in the beta cell- of the pancreas. · '!'his . uork is heing e xtended in ·the pigs and the release of hormones other than insulin-- is alsb being ex~ined.

Carbohydrate metabolism (Hilroshurst)

A survey was made of the lipid status of patie~ts attending the Diabetes Clinic and a favourable ~~sponse · to appropriate dietary ci~anges was. demonstrated.

It was shown . (with Reardon) in normal subjects that insulin given intravenously ~ncreased post-heparin lipoprotein lipase activity and variably increased plasma lipolytic activity. A similar trend was sho\'m by a small nwnber of diabetics tested.

TEACUil!G AND -OTHE? ACTIVITIES

During the year Dr Lloyd terminated his Postdoctoral Fellm'lship· to return to hospital clinical work in Adelaide and Dr B. Kudchodkar retun1ed to Canada. Dr Nelson joined the staff from Oklahoma to work with Dr Oenborough on muscle :inetabolism. Dr Julia Hickman ·(nee Potter) finished her Ph.Do ·work and ".iJill be t~':: ing up an appointment as a Lecturer in Pharmacology in the University of ~ 7estern Australia. nesearch scholars continuing into 1975 include Parissa Poulis, 11 oF. .. Reardon, Dr S . Chinayon from Ilangko){ and i ir Ho .l\kbar f ro!n l~arachi o · . '

Hembers of the Department participated in teaching and clinical activities at the Canberra and ~ Joden Valley Hospitals and lectured at Univers:ties and Hospitals elsewhereo They participated actively in national scientific meetings and on the cormnittees of various national academic and research organizations. Dr Fidge organized a course for senior students in the Department of Bioche111istry1 SGS, involving most of the members of Clinical Science.

Dr Ardlie participated in the American Heart Association meetings in Dallas, Texas and visited several lal:>oratories in North America. Dr Nestel was an invited participant in an International Symposium on Hutrition in Cardiovascular Disease held in Holland and Guest Lecturer for the Japanese Atherosc­lerosis Society. Professor Hhyte was a m.:mlber of t he Canberra Hospitals Fanagement Board and was involved in other aspects of health services development in the ACT and in the University's Feasibility Study for its proposed undergraduate medlcal school. He attended .. ammetting of the Co1iU!\i ttee on Hutri tion Surveys and ~urveil~~cer. -of t!1e.; :I~te~a;~i.o~a\ Uni~n of Nutritional Sciences in Delhi during · the -y3ar'· •. · . .......... ·. __ ·. . . . .

a. 12/1975

PUBLICATIONS

ARDLIE:;'~ ~J. G. and HAH , P. 1

· 0 Enzymatic basis for platelet aggregation and release: the significance of the platelet atmosphere. and the relationship between platelet function and blood coagulation'. British Journal of Haematology. 26, 331-356 (1974).

CLAi:rE I l'a .!!i. I 2 PRESSER' J. c. ' 2

!. Li\RITZ I v. a . 2 and DENBOROUGH, :!.A .

'Quantitative estimation of neutral anu amino sugars of glycoprotein from hwnan secretions by gas-liquid chromatography'. Biochemical i.1edicine 9, 342-353 (1974).

CLIFTON~BLIGH, P., 1 IIILLER, N.E. 1 and rmSTEL, P.J. 'Increased plasma cholesterol esterifying activity during colestipol resin therapy in man'. iletabolism 23, 4 37-4~4 (1974).

DBNB?ROUGH, L1 .A., 3 2~~ARNE , G.L., 2 ~10ULDS, R.F.TJ., 2 TSE, P. 2

and .:: lA..ll.TII:J, F. I. P... 'Insulin secretion in malignant hyperpyrexia.' British

: ~dical Journal 3, 49 3-495 (1974).

FIDGE, H. 'A reviet·1 of method::; and metabolic studies with the radioiodination of lipoproteins'. Chimica Acta 52, 5-13 (1974).

FIDGE, iJ . and POULIS, Parissa.

associated Clinica

'Studies on the radioiodination of very low density lipoprotein obtained from different mammalian species'. Clinica Chimica Act'! 52, 15 -,26 : (1974).

GOLDRICK, R.B. and GALTOH, D.J. 2

'Fatty acid synthesis de novo in human adipose tissue'. Clinical Science and !lolecular !:1edicine 46 , 469 -'179 (1974).

GOLDRICK, R.B.' IJESTEL, P.J. and IIAVZi..YSTEIN, Nathalie 'Comparison of a net-.r anorectic agent ·AN448 with fenfluramine in the treatment of refractory obesity'. :~dical Journal of Australia 1, 882-385 (1974).

GYORY, A.z., 2 EmJAHDS, K. D.G., 2 3TEt'7ART, J.H. 2 and :mYTE, H. 11 . 'Comprehensive one-day renal function testing in man'. Journal of Clinical Pathology 27, 382-391 (1974).

. .. . .

1Former member ·. t , .. .. ~ .· . . •

2Not a meml>e r of thin University

3aased on t-lork done prior .to joining this University .

12/1975

9.

HAN, P • l and APJ)LIE, N. G. 'Platelet aggregation and release by ADP and thrombin: Evidence i:>r two separate effects o_f ADP on platelets, involvement of fibrogen in release, and mechanism of inhibitory action of acetylsalicylic acid'. British Journal ·of ·Haematolo9y 26, 357-372 (12'74).

!IAIJ, P • 1 and A:IDLIE, u . G • 'The influence of pH, temperature and calcium on platelet aggregation: ; Iaintenance of environmental pH and platelet function for in vitro studies in plasma stored at 37°C. British Journal of Haematology 26, 373-389 (1974) •

HAN, P. 1 and ARDLIZ, il.G. 'Heparin, platelets and blood coagulation: Implications for low dose heparin prophylactic regimes in venous thrombosis'. British Journal of Haematology 27, 253-272 (1974).

HILLER, N.E. 1 and NESTEL, P.J. 'Triglyceride-lowering effects of chenodeoxycholic acid in patients with endogenous hypertriglyceridernia'. Lancet 2, 929-931 (1974).

BOULDS, n .• F.W. 2 and DBi:JBOROUGH, iJ .A. 3

'The biochemical basis of malignant hyperpyrexia'. British ~ 1edical Journal 2 7 241-2<14 (1974).

I10ULDS, R.F.N. 2 and DEHBOROUGH, Il.A. 3

'Identification of susceptibility to malignant hyper­pyrexia'. British Bedical Journal 2, 245-247 (1974) • .,

IlOULDS , n. F. H. ·~ and DEl:JBOROUGH , I1. A .3 'A study of tlle action of caffeine, halothane, potassiwn chloride and procaine on normal human skeletal muscle'. Clinical and Experimental Pharmacology and Physiology 1, 197-209 (1974).

NESTEL, P.J. 'Cholesterol metabolism in anorexia nervosa and hypercholesterolaemia'. The Journal of Clinical Endocrinology and iletabolism 28, 325-328 (1974).

NESTEL, P.J., HILLERv N.E. 1 and CLIFTON-BLIGH, P. 1 1 Plasma cholesterol esterification in vivo in man'. · Scandinavian Journal of clinical and laborato

upp •

1Former member

2Not a member of this University

3sased on work done prior to joining this University

I'. • 1:0 -. 12/1975 . \ .

NESTEL, P.J. and HUNTER, J.D. 1

'Bile acid excretion in man~ interrelated effects of · · Lyperlipidaemia and overweight'. Aust:r:alian .. and New

. . Zealand Journal of Uedicine 4 , 49 1-~~6 (1974).

NESTEL, P.J. ~ HAVENSTEIN, _l:1athalie·; SCOTT, T.H. -2 ~d COOI<, L.J. 2

'Polyunsaturated ruminant fats and cholesterol° metabolism in man'. A~stralian and New Zealand Journal of Iiedicine 4, ~97-501 (1974 •

HARD, c. Jane 3 " and HALiill :~ , D.G. 2

'Regulation of enzyme develQpment for glycerol utilisation by neonatal ·rat -liver'. Biology of the Neonate 2·3, ~03-413 (1973).

WILl1SHURST, E. G. 'The .management of obesity ·with diet and drugs'. Drug 'l'herapy ,·1, No.9, 7-17 (1973).

~ormer member 2 . Not a member of this University

3Based on work done prior to joining this University

...

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