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129 EFFECT OF DEPROTEINISED COW PLASMA ON HYDRATED, ALCOHOL- ANaeSTHETISED RATS *Not significant. t Significant (r<001). after insertion of the catheter, during which there were on the average two urine samples, a 1 litre blood-sample was removed through the catheter. The catheter was then removed, but the initial needle left in place, and through it an infusion of 30 ml. of 6% w/v dextran in physiological saline solution per kg. body-weight was given at a rate of 100 ml. per minute in four cows and at the rate of 40-50 ml. per minute in two cows. At the end of the infusion, the catheter was reinserted at the original site, and a second 1 litre sample was removed. All spontaneous urine voidings were collected during infusion, and the experiment was ended after two spontaneous voidings following infusion. Fig. 1 shows the reaction of the cow to dextran infusion at a rate of 100 ml. per minute. The location of the catheter tip was dictated by evidence suggesting that the source of the activity is the posterior hypothalamus.19-21 Cow urine was analysed for sodium and creatinine. Blood- samples, 1 litre each, were immediately deproteinised by the addition of 30% w/v trichloroacetic acid until a final concentra- tion of 5% of the acid was reached. After centrifugation of the precipitate, the supernatant was extracted with diethyl ether until the pH of the former had reached 6-5, at which point most of the trichloroacetate has been removed from the aqueous phase. The supernatant fluid was then kept at 4&deg;C, and samples were tested on hydrated, alcohol-anxsthetised rats by tech- niques described elsewhere. 22 We used seven animals in control tests; five of these and three different animals were used in the " treated " series, making ten animals in all. The injection volume was 0-2 ml., and 5-10 minute urine samples from the rats were analysed in the same manner as for the cow urine. RESULTS The rat-assay results are shown in the table and fig. 2. There was an insignificant tendency for control samples to decrease both rate of urine flow and sodium excretion in the assay animals, while experimental samples produced statistically significant increases in urine flow, sodium excretion and the tubular rejection fraction of sodium. It would seem that the cow, like the dog and cat, responds to extracellular fluid expansion with iso-osmotic, iso-oncotic dextran infusion by increasing sodium excretion, and that this response is also accompanied by the appearance of a natriuretic activity in the jugular venous plasma. Removal of two 1 litre blood-samples was obviously not a severe enough volume stress to a 500-700 kg. cow to alter the rate of sodium excretion to a sufficient degree to negate the effect of infusion. The natriuretic activity was present after precipitation of plasma proteins with trichloroacetic acid, which accords with the view 21 that the substance involved is of low molecular weight, probably a polypeptide. The sensitivity of the biological assay (i.e., activity measured in 0-2 ml. of diluted deproteinised plasma) indicates further that a separate saluretic principle is 19. Cort, J. H., Lichardus, B. Physiologia bohemoslov. 1963, 12, 300. 20. Lichardus, B., Mitro, A., Cort, J. H. Am. J. Physiol. 1965, 208, 1075. 21. Cort, J. H., Rudinger, J., Lichardus, B., Hagemann, I. ibid. 1966, 210, 162. 22. Cort, J. H. Electrolytes, Fluid Dynamics and the Nervous System; p. 201. London, 1965. involved, and that we are not dealing with a mere dilution effect of infusion on an antisaluretic activity. This is further supported by the fact that in two cows in which the total infusion dosage was administered at a rate of 40-50 ml. per minute instead of 100 ml. per minute this decreased gradient of volume expansion resulted in a very slight diuresis and natriuresis in the cows, and absence of a natriuretic activity in their plasma following infusion, despite an equivalent decrease in the cows hxmatocrit and plasma-protein concentrations. Assay of the same samples on the frog skin will be reported elsewhere. The cow would, therefore, seem to be an adequate model for attempts at isolating " natriuretic hormone," providing the advantage of large volumes of blood to serve as starting material. B. LICHARDUS M.D., C.SC. Bratislava Institute of Endocrinology, Academy of Science, Bratislava V. PLISKA B.SC. CHEM., C.SC. Prague Institute of Organic Chemistry and Biochemistry, Academy of Science, Prague V. UHRIN D.V.M., C.SC. Brno ’ T. BARTH B.SC. CHEM., C.SC. Prague Department of Anatomy and Physiology, School of Agriculture, Faculty of Agronomy, Nitra, Czechoslovakia Reviews of Books Preclinical Carcinoma of the Cervix Uteri Its Nature, Origin and Management. MALCOLM COPPLESON, M.D., F.R.C.O.G., King George V Memorial Hospital, Royal Prince Alfred Hospital, Sydney; BEVAN REID, M.D., B.V.SC., Queen Elizabeth Research Institute, University of Sydney; with the assistance of ELLIS PIXLEY, M.B., M.R.C.O.G., King Edward Memorial Hospital for Women, Perth, Western Australia. Oxford, New York, and Toronto: Pergamon Press. 1967. Pp. 321. E5;$15. THIS notable book is based on work which earned the two authors the Edgar-Gentilli prize of the Royal College of Obstetricians and Gynxcologists for 1967. From their own studies and from an exhaustive review of published work Coppleson and Reid challenge some commonly held views which, in their opinion, are based on insufficient or unsatis- factory evidence. They are critical of the reliance placed by clinicians on the reports given by cytologists and pathologists on smears and biopsies taken from the cervix. Here is an excellent corrective for those who believe and teach that exfoliative cytology and histopathology are precise techniques which lead to unequivocal diagnosis, reliable prognosis, and correct treatment in cases of so-called preinvasive cancer. The term " carcinoma-in-situ " is judged to be both ill advised and often unwarranted, for it implies that a form of cancer is already present and may well lead to unnecessary radical therapy. The true nature of many of the subtle cellular changes which take place in the cervical epithelium is unknown. Full- thickness loss of differentiation may well signify malignant potential, but in the individual case it is impossible to be certain about this. It is what the cells are doing rather than what they look like that matters; their dynamic function needs to be studied more closely. Many clinicians will share the authors’ anxiety about the widespread use of cone biopsy as a diagnostic measure, for this procedure is not without risk. Coppleson and Reid are skilled in the use of colposcopy and believe that this simple examination can be of great assistance in selecting areas of the cervix for biopsy, and even help the gynaecologist choose with assurance and safety those cases where local excision rather than hysterectomy is the treatment of choice. Not everyone will agree with their views on colposcopy; but it is difficult to argue with their conclusion that the true state of the cervix is best established by the combined use of several diagnostic tools, including colposcopy. This book with its critical appraisal of present knowledge and

Reviews of Books

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Page 1: Reviews of Books

129

EFFECT OF DEPROTEINISED COW PLASMA ON HYDRATED, ALCOHOL-ANaeSTHETISED RATS

*Not significant. t Significant (r<001).

after insertion of the catheter, during which there were on theaverage two urine samples, a 1 litre blood-sample was removedthrough the catheter. The catheter was then removed, but theinitial needle left in place, and through it an infusion of 30 ml.of 6% w/v dextran in physiological saline solution per kg.body-weight was given at a rate of 100 ml. per minute in fourcows and at the rate of 40-50 ml. per minute in two cows. Atthe end of the infusion, the catheter was reinserted at theoriginal site, and a second 1 litre sample was removed. All

spontaneous urine voidings were collected during infusion, andthe experiment was ended after two spontaneous voidingsfollowing infusion. Fig. 1 shows the reaction of the cow todextran infusion at a rate of 100 ml. per minute. The locationof the catheter tip was dictated by evidence suggesting thatthe source of the activity is the posterior hypothalamus.19-21Cow urine was analysed for sodium and creatinine. Blood-

samples, 1 litre each, were immediately deproteinised by theaddition of 30% w/v trichloroacetic acid until a final concentra-tion of 5% of the acid was reached. After centrifugation of theprecipitate, the supernatant was extracted with diethyl etheruntil the pH of the former had reached 6-5, at which point mostof the trichloroacetate has been removed from the aqueousphase. The supernatant fluid was then kept at 4&deg;C, and sampleswere tested on hydrated, alcohol-anxsthetised rats by tech-niques described elsewhere. 22 We used seven animals in controltests; five of these and three different animals were used in the" treated " series, making ten animals in all. The injectionvolume was 0-2 ml., and 5-10 minute urine samples from therats were analysed in the same manner as for the cow urine.

RESULTS

The rat-assay results are shown in the table and fig. 2.There was an insignificant tendency for control samples todecrease both rate of urine flow and sodium excretion inthe assay animals, while experimental samples producedstatistically significant increases in urine flow, sodiumexcretion and the tubular rejection fraction of sodium.

It would seem that the cow, like the dog and cat,responds to extracellular fluid expansion with iso-osmotic,iso-oncotic dextran infusion by increasing sodium

excretion, and that this response is also accompanied bythe appearance of a natriuretic activity in the jugularvenous plasma. Removal of two 1 litre blood-sampleswas obviously not a severe enough volume stress to a

500-700 kg. cow to alter the rate of sodium excretion toa sufficient degree to negate the effect of infusion.The natriuretic activity was present after precipitation

of plasma proteins with trichloroacetic acid, whichaccords with the view 21 that the substance involved is oflow molecular weight, probably a polypeptide.The sensitivity of the biological assay (i.e., activity

measured in 0-2 ml. of diluted deproteinised plasma)indicates further that a separate saluretic principle is

19. Cort, J. H., Lichardus, B. Physiologia bohemoslov. 1963, 12, 300.20. Lichardus, B., Mitro, A., Cort, J. H. Am. J. Physiol. 1965, 208, 1075.21. Cort, J. H., Rudinger, J., Lichardus, B., Hagemann, I. ibid. 1966, 210,

162.22. Cort, J. H. Electrolytes, Fluid Dynamics and the Nervous System;

p. 201. London, 1965.

involved, and that we are not dealing with a mere dilutioneffect of infusion on an antisaluretic activity. This isfurther supported by the fact that in two cows in whichthe total infusion dosage was administered at a rate of40-50 ml. per minute instead of 100 ml. per minute thisdecreased gradient of volume expansion resulted in a veryslight diuresis and natriuresis in the cows, and absence of anatriuretic activity in their plasma following infusion,despite an equivalent decrease in the cows hxmatocrit andplasma-protein concentrations. Assay of the same

samples on the frog skin will be reported elsewhere. Thecow would, therefore, seem to be an adequate model forattempts at isolating " natriuretic hormone," providingthe advantage of large volumes of blood to serve as

starting material.B. LICHARDUS

M.D., C.SC. BratislavaInstitute of Endocrinology,

Academy of Science, Bratislava

V. PLISKAB.SC. CHEM., C.SC. Prague

Institute of OrganicChemistry and Biochemistry,Academy of Science, Prague

V. UHRIN

D.V.M., C.SC. Brno

’ T. BARTHB.SC. CHEM., C.SC. Prague

Department of Anatomy and Physiology,School of Agriculture,Faculty of Agronomy,Nitra, Czechoslovakia

Reviews of Books

Preclinical Carcinoma of the Cervix UteriIts Nature, Origin and Management. MALCOLM COPPLESON,M.D., F.R.C.O.G., King George V Memorial Hospital, RoyalPrince Alfred Hospital, Sydney; BEVAN REID, M.D., B.V.SC.,Queen Elizabeth Research Institute, University of Sydney;with the assistance of ELLIS PIXLEY, M.B., M.R.C.O.G., KingEdward Memorial Hospital for Women, Perth, WesternAustralia. Oxford, New York, and Toronto: PergamonPress. 1967. Pp. 321. E5;$15.

THIS notable book is based on work which earned the twoauthors the Edgar-Gentilli prize of the Royal College ofObstetricians and Gynxcologists for 1967. From their ownstudies and from an exhaustive review of published workCoppleson and Reid challenge some commonly held viewswhich, in their opinion, are based on insufficient or unsatis-factory evidence. They are critical of the reliance placed byclinicians on the reports given by cytologists and pathologistson smears and biopsies taken from the cervix. Here is anexcellent corrective for those who believe and teach thatexfoliative cytology and histopathology are precise techniqueswhich lead to unequivocal diagnosis, reliable prognosis, andcorrect treatment in cases of so-called preinvasive cancer.

The term " carcinoma-in-situ " is judged to be both ill advisedand often unwarranted, for it implies that a form of cancer isalready present and may well lead to unnecessary radical

therapy. The true nature of many of the subtle cellular changeswhich take place in the cervical epithelium is unknown. Full-thickness loss of differentiation may well signify malignantpotential, but in the individual case it is impossible to becertain about this. It is what the cells are doing rather thanwhat they look like that matters; their dynamic function needsto be studied more closely. Many clinicians will share theauthors’ anxiety about the widespread use of cone biopsy as adiagnostic measure, for this procedure is not without risk.

Coppleson and Reid are skilled in the use of colposcopy andbelieve that this simple examination can be of great assistancein selecting areas of the cervix for biopsy, and even help thegynaecologist choose with assurance and safety those cases

where local excision rather than hysterectomy is the treatmentof choice. Not everyone will agree with their views on

colposcopy; but it is difficult to argue with their conclusionthat the true state of the cervix is best established by thecombined use of several diagnostic tools, including colposcopy.This book with its critical appraisal of present knowledge and

Page 2: Reviews of Books

130

practice, its contribution of original work, and extensive reviewof the literature will be a valuable addition to the shelves of

personal and of departmental libraries. The numerous

illustrations are good.

Basic Techniques in Human Metabolism and RespirationG. J. R. MCHARDY, M.A., B.SC., B.M., M.R.C.P., consultant

physiologist, City Hospital, Edinburgh; D. SHIRLING, technicalresearch assistant, Western General Hospital, Edinburgh; R.PASSMORE, M.A., D.M., reader, department of physiology, Uni-versity of Edinburgh Medical School. Oxford: BlackwellScientific Publications. 1967. Pp. 64. 7s. 6d.

ALTHOUGH accounts of these techniques are to be found inseveral large books on chemical and physiological methods, oneof the most usual sources has been Douglas and Priestley’slittle book, which is, unfortunately, now out of print. This isa worthy successor. Copies of it should be scattered aroundthe laboratory, and it will be a great help in the conduct ofundergraduate practical classes. Very good value for money.

Proceedings of the Fifth International Congress ofNeuropsychopharmacology

Editors: H. BRILL, West Brentwood, N.Y.; J. 0. COLE, Boston,Mass.; P. DENIKER, Paris; H. Hippuss, Berlin-Charlottenburg;P. B. BRADLEY, Birmingham. The Hague: Mouton & Co.1967. Pp. 1278. D. fl. 187.20;$52; E21 15s.

THIS massive tome records the proceedings of the 5thInternational Congress of the C.I.N.P. in March, 1966, inWashington. Its 1278 pages contain nearly 250 contributionsin German, English, and French on most aspects of psycho-pharmacology. The text is divided into 14 sections whichinclude material on basic methodological problems, animaltest models, pharmacological and biochemical actions, andtoxic and milieu effects. In addition special problems dis-cussed include drug effects on memory, drug abuse, and therelation of classical conditioning to psychopharmacology. Theeditors have accomplished a formidable task in a relativelyshort time; but one can still wish they had insisted on a linguafranca at least for summaries, and had included some of thediscussions which took place. This volume is attractivelyset out, well printed, and concisely indexed, but is probablypriced beyond the reach of any but the larger specialistlibraries.

Rhinoviruses

Monographs in Virology: Vol. 1. DOROTHY HAMRE, PH.D.department of medicine, University of Chicago, Chicago,department of medicine. University of Chicago, Chicago,Illinois. Basle and New York: S. Karger. London: AcademicPress. 1968. Pp. 88. Sw. fr./DM 20.50;$4.90.

THE first viruses of this group were cultured just over 10years ago. The author has contributed a great deal to ourknowledge of the epidemiology and serotyping of these

organisms. These aspects are particularly well treated here,and previously unpublished information is included. Thereare also sections on the properties of the virus particle, onmethods of virus cultivation, and on vaccination, but littleabout pathological changes. Virtually every publication isreferred to, and many are quite fully summarised. Thisreview would be useful to an epidemiologist or virologist, or toanyone else who wanted to get abreast of the literature. Ifthe academic and production standards are maintained, thisvolume marks the beginning of a valuable new series.

The Placenta in Twin PregnancyS. J. STRONG, Gibson Laboratories, Radcliffe Infirmary,Oxford; G. CORNEY, department of paediatrics, Radcliffe

Infirmary, Oxford. Oxford, New York and Toronto: Per-

gamon Press. 1967. Pp. 134. E5 5s.;$16.THIS is an important contribution to the study of twin

pregnancy. The two authors have themselves carried out a

comprehensive study of twin conception, placentation,vascular relationships, and zygosity determination. As

happens so often when a subject is studied in depth, theyquickly recognised that many settled beliefs are based on falseassumptions, conjecture, and conflicting evidence. Their

own methodical and painstaking investigations have helped todistinguish fact from fiction; and their monograph will appealwidely to clinicians, pathologists, geneticists, and otherresearch workers. A very full bibliography is given in anhistorical section at the beginning of the book. There aresections on the development of twin placentx, on the fre-

quency and nature of vascular communications between the

placentx, and on the effect that these may have on the intra-uterine and subsequent life of the twins The book is beauti-

fully produced, and lavishly illustrated. It will prove an

excellent work of reference for all interested in the subject.

Economic Analysis for Health Service EfficiencyEconometric Studies of the British National Health Service.MARTIN S. FELDSTEIN, Harvard University. Amsterdam:North Holland Publishing Company. 1967. Pp. 322. E5.

THE main part of this book is an attempt to apply certainmethods of economic analysis to the National Health Service.It is therefore largely technical and no doubt could providestudents of econometrics with the means to pass many happyhours in following, perhaps even occasionally disputing, theapplication of mathematical methods to a mass of financialand associated data on the N.H.S., the collection, collation,and use of which are impressive. The last chapter presents" a non-technical summary of the major conclusions of policy

relevance ". In the event, this adds sadly little to the sum ofknowledge about the N.H.S.

The Royal ApothecariesLESLIE G. MATTHEWS. London: Wellcome Historical MedicalLibrary. 1967. Pp.191. 25s.

THE Society of Apothecaries played an important part in thedevelopment of both pharmacy and the general practice ofmedicine in England and Wales. In December the Societycelebrated the 350th anniversary of the granting of its firstcharter separating the Apothecaries from the Grocers’ Com-pany. Like the Society, the Royal Apothecaries have gonethrough several transitions from the time of William

Speciarius (Spicer to King John, appointed 1207) to the

physicians and surgeons holding posts of Apothercary or

Surgeon-Apothecary to members of the Royal Family today.The early apothecary spicers and apothecaries supplied a

variety of items such as medicines, dried fruits, spiced wines,and confectionery. Over several centuries they were

responsible for preparing the anointing-oil’for coronations andfor embalming the bodies of deceased sovereigns. They werealso, over a long period, present at both the births and deathsof members of the Royal Family. In the Stuart period wefind the Royal Apothecaries, although still predominantlypharmaceutical, tending towards medicine: for example,William Rosewell received a Lambeth M.D. in 1765 as did JohnJones in 1677. Mr. Matthews’ book gives a fascinatingaccount of the lives and fortunes of the Royal Apothecariesand incidentally gives much information about the typesand costs of drugs and other commodities and other details ofcourt and London life over a long period. It is well docu-mented and annotated.

New Editions

Principles of Gynaecology.-3rd ed. By T. N. A. Jeffcoate.London: Butterworths. 1967. Pp. 971. E6 10s.

Textbook of Surgery.-2nd ed. Edited by David A. Macfarlaneand Lewis P. Thomas. Edinburgh and London: E. & S. Living-stone. Baltimore: Williams & Wilkins Co. Toronto: Macmillan

Company of Canada. 1968. Pp. 770. 60s. ;$10.75 (Canada).Care of the Patient in Surgery: Including Techniques.-4th ed. By

E. L. Alexander, Wanda Burley, Dorothy Ellison, and RosalindValleri. London: Henry Kimpton. St. Louis: C. V. Mosby Co.1967. Pp. 898. E7 12s.;$16.85.

A Synopsis of Public Health and Social Medicine.-2nd ed. By A. J.Essex-Cater. Bristol: John Wright & Sons. Baltimore: Williams &Wilkins Co. Toronto: Macmillan Company of Canada. 1967. Pp.740. 75s.