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gastric ulcer patients, 3,6,7 thus only the antrum may beaffected by reflux, leaving the parietal cell populationundamaged and capable of hypersecretion. A prolongedstimulus from the antrum caused by recurringduodenogastric reflux would produce sustained hypergas-trinaemia and explain the increased parietal cell mass,’8 asuggestion supported by the finding that patients withduodenal ulceration have a small alkaline field16 and noevidence of gastritis in the body of the stomach.","Moreover, transplantation of the antrum into the jejunumleads to inflammation of the antral mucosa and an increase inthe parietal cell mass in the body of the stomach.35 Thiscombination of antritis and increased parietal cell mass is alsoseen in patients with duodenal ulcer, which again suggeststhat these changes may be produced by reflux of duodenalcontents.

All the pathophysiological changes that occur in patientswith duodenal ulcers can be explained by the retlux

hypothesis, especially if alkaline reflux should suppresssomatostatin and stimulate gastrin release. The involvementof somatostatin is supported by the finding that infusions ofthis hormone can prevent the development of duodenal ulcersin cats36 while alkalinisation of the antrum reduces antralvenous somatostatin immunoreactivity and increases gastrin

1

activity.26 The normal ratio of antral "G" (gastrin) to "D"(somatostatin) cells is 7:1 . This relation alters in duodenalulceration; ratios may reach 90:1 in cases associated with "G"cell hyperplasia,37 while the "D" cell count in the duodenummay fall. 38

This work was done whilst a Bernard-Sunley Fellow at the Royal College ofSurgeons of England and has formed the basis of an M.S. thesis for LondonUniversity.

I thank Prof. D.E.M. Taylor for his helpful guidance and criticism, andProf. R.C.N. Williamson and Mr. M.H. Thompson for their advice on themanuscript.

REFERENCES

1. Fiddian-Green RG. Is peptic ulceration a hormonal disease? Lancet 1977; i: 74-77.2. Bonnevie, O. Gastric and duodenal ulcers in the same patient. Scand J Gastroenterol

1975; 10: 657-64.3. Capper WM, Airth GR, Kilby JO. A test for pyloric regurgitation. Lancet 1966, ii,

621-23.

4. Capper WM. Factors in the pathogenesis of gastric ulcer. Ann Roy Coll Surg Eng 1967;40: 21-35.

5. Rhodes J, Barnardo DE, Phillips SF, Rovelstad RA, Hofmann AF. Increased reflux ofbile into the stomach in patients with gastric ulcer. Gastroenterology 1969, 57:241-52.

6. Flint FJ, Grech P. Pyloric regurgitation and gastric ulcer. Gut 1970; 11: 735-37.7. Wormsley K. Aspects of duodeno-gastric reflux in man. Gut 1972; 13: 243-50.8. Fisher RS, Cohen S. Pyloric sphincter dysfunction in patients with gastric ulcer. N

Engl J Med 1973; 288: 273-76.9. Fiddian-Green RG, Russell RCG, Hobsley M. Pyloric reflux in duodenal ulceration

and its relationship to smoking. Br J Surg 1973; 60: 321.10. Du Plessis DJ. Pathogenesis of gastric ulceration. Lancet 1965; i: 974-78.11. Lawson HH. Gastritis and gastric ulceration. Br J Surg 1966; 53: 493-96.12. Ritchie WP, Delaney JP. Susceptibility of experimental atrophic gastritis to

ulceration. Gastroenterology 1971; 60: 554-59.13. Oi M, Ito Y, Kumagi F, et al. A possible dual control mechanism in the origin of peptic

ulcer A study on ulcer location as affected by mucosa and musculature.Gastroenterology 1969; 57: 280-93.

14. Kimura K. Chronological transition of the fundic-pyloric border determined bystepwise biopsy ofthe lesser and greater curvatures ofthe stomach. Gastroenterology1972; 63: 584-92.

15. Du Plessis DJ. The importance ofthe pyloric antrum in peptic ulceration. S Afr J Surg1963; 1: 3-11.

16. Capper WM, Laidlaw CDA, Buckler K, Richards D. The pH fields of the gastricmucosa. Lancet 1962; ii: 1200-02.

17. Capper WM, Butler TJ, Buckler KG. New alkaline areas in gastric mucosa aftergastric surgery. Gut 1966; 7: 220-22.

18. Guiss LW, Stewart FW. Histologic basis for anacidity in gastric disease. Arch Surg1948, 57: 618-23.

19. Ball PAJ, James AH. The histological background to gastric ulcer. Lancet 1961; i:

1365-67.20. Thomas WEG. Functional changes in acid secretion produced by duodeno-gastric

reflux. Gut 1980; 21: 413-17.21. Thomas WEG. Serum gastrin levels in duodenal reflux and the control state. Gut 1979;

20: 918.

22. Thomas WEG. A study of the effects of duodenal reflux in the dog, MS thesis, 1980London University.

23. Elde R, Hokfelt T, Johansson O, Schultzberg M, Effendic S, Luft R Cellularlocalisation of somatostatin. Metabolism 1978; 27 (9 suppl 1): 1151-59

24. Raptis S, Dollinger HC, Von Berger L, Schlegel W, Schroder KE, Pfeiffer EF Effectsof somatostatin on gastric secretion and gastrin release in man. Digestion 1979, 13:15-26.

25 Barros D’Sa AAJ, Bloom SR, Barn JH. Direct inhibition of gastric acid by growth ho:mone release-inhibiting hormone in dogs. Lancet 1975, i: 886-87

26.Gustavsson S, Lundqvist G. Antral somatostatin and gastrin release VI World

Congress of Gastroenterology, Madrid 1978, 62 (abstract).27. Thomas WEG. Effects of somatostatin in duodenal reflux and the control state Br J

Surg 1979; 66: 354.28. Munk J, Hoare M, Kirk CJC, Johnson AG. Effects on pyloric reflux of antral and

duodenal pacing in the cat. Gut 1978; 19: 996-97.29. Nagamachi Y, Skoryna SC. Relationship between gastric mucosal pH and site of peptic.

ulceration. Am J Surg 1977; 133: 593-96.30. Baron JH. The clinical use of gastric function tests Scand J Gastroent 1970; 5 (suppl.

6); 9-46.31. Byrnes DJ, Young JD, Chisholm DJ, Lazarus, L. Serum gastrin in patients with peptic

ulceration. Br Med J 1970 ii; 626-29.32. McGuigan JE, Trudeau WL. Differences in rates of gastrin release in normal persons

and patients with duodenal ulcer disease. N Engl J Med 1973, 288: 64-66.33. Malagelada JR, Longstreth GF, Deering TB, Summerskill WHJ, Vay Liang WG.

Gastric secretion and emptying after ordinary meals in duodena ulcer.

Gastroenterology 1977; 73; 989-94.34. Johnston D, Jepson K. Use of pentagastrin in a test of gastric acid secretion. Lancet

1967, ii; 585-88.35. Butler BA, Cheng JWB, Ritchie WP, Delaney JP. Antral gastritis and parietal cell

hyperplasia. Fed Proc 1970; 29; 255.36. Konturek, SJ, Radecki, T, Pucher A, Coy DH, Schally AV. Effect of somatostatin on

gastrointestinal secretions and peptic ulcer production in cats Scand J Gastroent1977; 12: 379-83.

37. Polak JM, Bloom SR, Bishop AE, McCrossan MV. ’D’ cell pathology in duodenalulcers and achlorhydria. Metabolism 1978, 27 (9 suppl.1), 1239-42

38. Polak JM, Bloom SR, McCrossan, MV, Arimura A, Pearse AGE Morphology ofsomatostatin in gastrointestinal health and disease. Gut 1976, 17: 816.

Reviews of Books

Endocrinology and Cancer

Clinics in Endocrinology and Metabolism, vol. IX, no. 2. Edned by K.7-Abe, National Cancer Center Research Institute, Tokyo. London a::, ,:Abe, National Cancer Center Research Institute, Tokyo. London a::Philadelphia: W. B. Saunders. 1980. Pp. 433. £ 9.

HORMONE production is increasingly being recognised as a muchmore universal concomitant of neoplasia than simply the well-recognised syndromes of paraneoplasia that occur in associationwith carcinoma of the bronchus. A framework for understandingthis phenomenon has been proposed in the APUD concept. Theacronym was first applied in 1968 to widely distributed cells thatcould take up amine precursors (such as dopa or 5-hydroxyirypto-phan) and decarboxylate them to produce biogemc amines

(catecholamines or serotonin). Despite their amine-handlingcharacteristics expressed by the acronym (Amine Precursor Uptakeand Decarboxylation), the primary function of many of these cellsnow seems to be the production not of biogenic amines but of low-molecular-weight polypeptides, some of which are knownhormones (e.g., corticotrophin, insulin, glucagon, calcitonin). Thediffuse distribution of the APUD cells in neurons and endocrinecells, and the multiplicity of their products (35 APUD peptides havenow been defined), mean that such diverse clinical syndrome ashyperadrenalism due to oat-cell carcinoma of the lung, multipleendocrine neoplasi (MEN), carcinoid tumour, phaeochromo-cytoma, Zollinger-Ellison syndrome, hypercalcaemia, (due to ec-topic parathyroid hormone production), and hypoglycaemia (due toectpic insulin-like secretion) can now be viewed as derangements ofneuroendocrine function-specifically of the APUD cells.This volume is concerned in large measure with apudomas.

including the three new endocrine pancreatic tumour syndromes-glucagonomas, VIP(vasointestinal polypeptide)omas, and

somatostatinomas. The basic concept and current status of APUDcells are clearly explained. Ectopic hormone syndromes are exam-

1169

ined in the light of current developments in knowledge abouthormone precursors, from the well-known big gastrin to pro-PTHand pre-proinsulin; it now seems that all these precursors are

cleaved to yield their active hormones by similar proteolyticcleavage mechanisms. Hypercalcaemia of cancer (includingmechanisms, assessment, and treatment) is critically examined, andthe excellent chapter on tumour hypoglycaemia includes a lucidexposition of present views on the insulin-like components of serumthat do not react with anti-insulin antibodies (the so-called non-suppressible insulin-like activity or NSILA of serum).The remainder of the volume gives the current management of

prostatic carcinoma, reviews the value of hormone receptormeasurement in breast cancer therapy, and discusses the difficultsubject of treatment of metastatic thyroid cancer. The last chapter,which examines in detail endocrine disorders following irradiationor chemotherapy and tabulates the data from many useful referenceson the subject, reveals an unexpectedly high incidence of iatrogenicdisease in cancer patients treated by irradiation or chemotherapy. Ata time when combined-modality treatment of some solid tumours isbeginning to produce long-term survivors, this chapter is not onlyinformative but timely.Several of the pioneers in the field, including A. G. E. Pearse,

Stephen Bloom and Julia Polak, all of APUDoma renown, andW. L. McGuire, well known for his work on oestrogen receptors,have contributed to this volume. The result is a lucid, up-to-date,and easy-to-read account of the fascinating developments (includingclinical management) in this rapidly advancing area. The volumecan be highly recommended to those in general medicine andsurgery as well as to oncologists.Cancer Research Unit,Royal Victoria Infirmary,Newcastle upon Tyne J. A. DICKSON

Prevention of Venous Thrombosis and PulmonaryEmbolism

J. G. Sharnoff, Mount Vernon Hospital, New York. Lancaster: M. T. P.Press. 1980. Pp. 135. f8.95.

IN 1962 Dr J. G. Sharnoff described the first study of the effect oflow-dose subcutaneous heparin in preventing postoperativethromboembolism. This was based on his observations of plateletbehaviour and coagulation in patients in whom venous thrombosisdeveloped. An important aspect was the regular monitoring of co-agulation times for which he developed a modification of the Dale-Laidlaw coagulometer. The basic concept of subcutaneous heparinprophylaxis was eagerly taken up by many workers, particularlythose at King’s College Hospital, London, none of whom con-sidered that monitoring was necessary. There have been scatteredreports of bleeding in patients on a fixed-dose regimen, and contro-versy about its safety has continued. Dr Sharnoffhas taken little partin the controversy, other than writing a few letters to The Lancet.This monograph is essentially a defence of his monitored heparinregimen and a criticism of the fixed dose regimen which is now sopopular withsurgeons.The introductory chapters are a standard account of the epidemio-

logy and pathology of thrombosis, the pharmacology of platelets,and the many properties of heparin. Mechanical methods ofpreven-tion are only briefly mentioned and without reference to their origi-nators, and low molecular weight dextran gets a little better con-sideration. The diagnosis and treatment of established venousthrombosis is described adequately. Most of the attention is given tothe author’s own studies and a detailed criticism of many studiesusing the fixed-dose regimen. This includes the controversy sur-rounding the 1975 multicentre study. The chapter on preventionconcludes: "it is clear from the evidence presented that in the fore-seeable future it is advisable for the author’s ... regime of heparinprophylaxis to be the method against which all other prophylacticmethods for the prevention of thromboembolism are measured". Itis a great pity that there is less evidence to support this statementthan the many controlled studies which have employed the fixed-dose regimen. A study of 3000 patients undergoing thoraco-abdominal surgery is described but, as in the author’s original study,

this does not seem to be controlled and blood loss is not mentioned.Another study, of patients undergoing prostatectomy, showedincreased blood loss, even with monitoring, but we are not toldwhether this was dangerous or of nuisance value only, nor how theregimen used compares with the fixed-dose heparin regimen.Dr Sharnoff has made a most important contribution to the safety

of surgery. It only needs a little more work for the final validation ofhis method. Regretfully, recent observations of saline infusion as athrombogenic agent and the use of intravenous ultra-low-doseheparin were published while this book was going to press and couldnot therefore be included in Dr SharnofPs argument. Apart fromthis, the book provides a fascinating and up-to-date insight into thecontroversies surrounding subcutaneous low-dose heparin.

Department of Surgery,Lewisham Hospital, London DAVID NEGUS - .

BromocriptineA Clinical and Pharmacological Review. Edited by Michael O. Thorner,University of Virginia School of Medicine, Charlottesville, Virginia, E.Fluckiger, Sandoz Ltd., Basle, and Donald B. Calne, Naational Instituteof Neurology and Communicative Disorders, Bethesda, Maryland. NewYork: Raven. 1980. Pp. 181.$29.92.

THE pages of this clearly-written, massive literature review arepacked full of information. Three experts in pharmacology, neuro-pharmacology, and endocrinology provide: first, accounts of

gonadotrophin physiology, hyperprolactinaemia and acromegaly,and the mechanisms of action and clinical use of bromocriptine;next, a detailed review ofparkinsonism and a thorough discussion ofthe therapeutic use of bromocriptine; and finally an extensive phar--macological review of bromocriptine, which also deals with adversereactions. The layout is excellent; the scope of each chapter isindicated at the beginning, each chapter ends with a full list ofreferences (that on pharmacology has 178 references), mostlygleaned from the 1970s and particularly 1979, and there is a subjectindex for the entire book. The book will be invaluable to researcherswho deal with the basic pharmacology of the drug or the clinical con-ditions treatable with bromocriptine. For the neurologist andclinical endocrinologist who is interested primarily in the practicalaspects of treatment of patients with parkinsonism, or with pituitarytumours secreting mainly prolactin or growth hormone, it providesuseful background reading. There is a great deal more in this bookthan the title suggests. For example, the first chapter is concernedsolely with the very topical subject of the interrelationships of thenervous and endocrine systems, with reference to drugs other thanbromocriptine used to augment dopamine activity; and the bookalso deals at length with the mechanisms of diseases apart from therole of bromocriptine.Department of Medicine, I

Royal Postgraduate Medical School,London G. F. JOPLIN

Neonatal HyperbilirubinemiaMonographs in Neonatology. Gerald B. Odell, University of Wisconsin,Madison, Wisconsin. New York and London: Grune and Stratton. 1980.Pp. 153.$16.50.

THIS monograph is a lucid summary of neonatal bilirubinmetabolism from the viewpoint of a paediatrician who has both donelaboratory work in this subject and been prominent in the criticalassessment of therapy. It covers the complex physical chemistry ofbilirubin and the physiology of its formation and excretion in bothfetal and neonatal life. Unfortunately, Dr Odell does not make itclear whether he is reporting data from man or from small labora-tory animals in which transient neonatal hyperbilirubinaemia doesnot occur. In the discussion of the multifactorial causes of neonatal

- hyperbilirubinaemia prominence is given to the evidence that majorcontributory factors are the liver’s inability to clear bilirubinbecause of the perinatal oestrogen load and the increased entero-hepatic circulation of bilirubin at that time. Amongst many inter-

1170

esting comments on pathological factors adversely affectingbilirubin metabolism is the conclusion that jaundice is a rare andusually late cardinal sign of sepsis. In the assessment of the risk ofneurotoxicity from bilirubin the empirical level of serum uncon-jugated bilirubin above which there is a significant risk of kernic-terus is still said to be 20 mg/dl. Although the author is satisfied thatin a research setting tests which measure the reserve capacity ofalbumin to bind bilirubin in vitro allow better identification of risksof neurotoxicity than serum unconjugated bilirubin levels, none ofthe tests can be recommended for routine clinical use.The author gives clear guidelines for the place of exchange trans-

fusion, with or without prior administration of albumin. Full detailsare given of the biochemical action of phototherapy on bilirubin andof the complications associated with the use of such therapy inneonates. No attempt is made to analyse the many clinical studies ofphototherapy with a view to giving some guidelines on the in-dications and optimum duration of treatment. The author simplystates that these aspects of phototherapy require better definition.The author is concerned by the potential delayed hazards of photo-therapy and urges that well-designed properly monitored studies beundertaken to define the ultimate role of phototherapy in thecontrol of neonatal hyperbilirubinaemia. By citing "a recent prelim-inary report" which indicates a "greater neonatal mortalityassociated with its use in premature infants" Dr Odell has guar-anteed for himself a continuing place in the controversy surround-ing the efficacy and safety of phototherapy.Despite these minor reservations, I can recommend this book as a

critical comprehensive reference work for both laboratory workersand paediatricians concerned with the neonate and bilirubinmetabolism.

Department of Child Health,Kings College Hospital Medical School,London ALEX P. MOWAT

Disasters-Medical OrganisationEdited by Jan de Boer and Thomas W. Baillie, District Hospital,Warnsveld, Holland. Oxford and New York: Pergamon Press. 1980. Pp.110.$14.50.

THIS seventeen-author book, translated from Dutch into English,is not the lightest of medical reading, but for those responsible fordisaster planning and management, it is essential reading. The firstfour chapters deal with questions of authority and organisation atmunicipal and provincial level. The book seems to recommend asingle strategy for simple disasters, where the community is intact(e.g., railway accidents); compound disasters, where the communityis disrupted; and nuclear war, which is a very specialised form ofcompound disaster. Of these the simple disaster is by far thecommonest in the Netherlands, as in the United Kingdom, but theplans recommended overburden senior officers of emergencyservices by structures for coordinating many government depart-ments. These structures seem much more suitable for compound ornuclear disasters. This book, of course, is not responsible for thelegislation which it describes, but in the Netherlands some of thelegislation was amended in 1975.The excellent accounts of disasters concerning the railways, inter-

national airport, europort, and chemical factory have the authenticring of experience. However, the civil defence and Red Crossdescribe their involvement in each case as if their own rescue organi-sation was the only one present, and the ambulance service wouldconfine its interest entirely to the transport of patients. Their plansseem more suited to nuclear attack than to simple disasters.The model disaster plan for a middle sized district hospital will be

welcomed by similar hospitals in many countries. The detailcontained in its forms and diagrams will be particularly useful. Thefirst half of the discussion, on the sorting of patients (called triage),follows a traditional line, and achieves little more clarity than mostprevious attempts. The second half breaks new ground with itsdiscussion of how the "injury severity score" might be of use in thesorting of disaster patients. The guidelines for simplifying surgeryand anaesthetics during disasters might have been more successful ifthey had concentrated more on general principle and less on specific

advice. In a disaster I would not call a neurologist for cases ofconcussion, and for almost all scalp wounds I would clean andsuture rather than excise and leave open as advised. For pain controlin disasters, I am surprised to find no mention of ’Entonox’.Although there are many more details on which I take issue. I h4; had great difficulty in writing a short review, and this is a sign offimportant book.

Accident & Emergency Department,Royal Victoria Hospital, Belfast WILLIA.M. H RUTHERFOD

Body ImageA Surgical Perspective. Frederick M. Grazer and Jerome R. Klingbeu.University of California School of Medicine, Irvine, Cahforma S[Louis: C. V. Mosby. 1980. Pp. 422. £46.

THIS book on, basically, cosmetic surgery covers a range of dis-connected subjects from the history of costume, via the psychologl’cal aspects of body image, to detailed operative procedures. It wasclearly intended for North American surgeons, but the level atwhich the chapters are pitched is very varied. Some chapters wouldbe of interest and use to the expert, but at least one chapter, on theanatomy of the skin, is suitable for preclinical students.

I have considered its use to me, a trainee plastic surgeon. Thechapters on the history of body change I did not find interesting, andnot nearly as good as the work of Michael Ayrton’s The ChangingFace of Beauty. The sections on preoperative counselling were ofinterest, at least to see how much is advised in North America.Knowing that in Britain it is not possible to have two or three longpreoperative interviews, I wonder if we are not too brusque, andwhether the few minutes given to each patient, at least in theNational Health Service, are not too little for making the patientunderstand what he or she is agreeing to have done. The chapter onanaesthesia illustrates the variability of practice on the two sides ofthe Atlantic even more clearly. This is followed by the most usefulpart of the book; abdominoplasty, thigh-plasty, and brachioplasty.each receiving a separate chapter. Each starts with an exhaustive butnon-critical historical background to the procedure and then beauti-fully illustrated and accompanied by photographs, give very fulldetails of the author’s operations. The detail is such that I now feelthat not only would I be much happier attempting any of theseprocedures, but also, and more importantly, that I could make arational decision as to the most appropriate operation or modifica-tion for individual cases.

My main criticism is that cosmetic surgery of the breast, which isadvancing very rapidly is not included, particularly as several

chapters could have been drastically reduced or discarded with verylittle overall loss. In summary, this is a useful reference book for the

junior plastic surgeon and, I would expect, an interesting read forthe expert.

St. Luke’s Hospital,Bradford, West Yorkshire A. H. N. ROBERTS

New Editions

The House Physician’s Handbook.-5th ed. By C. Allan Birch, S. J. Surtee..and Richard Wray. Edinburgh: Churchill Livingstone. 1980. Pp. 209 £495

Gynecologic Endocrinology.-3rd ed. Echted by Jay Gold and John BJoslmovich. London: Harper & Row. 1980. Pp. 914. 40.75.Manual of Clinical Immunology.-2nd ed. Edited by N R Rose & H

Friedman. Washington DC: American Society for Microbiology 1980 P,-1105.$25.00 (cloth);$21.00 (flex).The Epilepsies.-3rd ed. By John M. Sutherland & Mervyn J J Eac

Edinburgh: Churchill Livingstone. 1980. Pp. 156. 3.95.The Diagnosis of Stupor & Coma.-3rd ed. By Fred Plum & Jerome E

Posner. Philadelphia: F. A. Davis Co. 1980. Pp. 373.$27.50Gray’s Anatomy.-36th ed. Edited by Peter L. Williams & Roger ::,

Edinburgh: Churchill Livingstone. 1980. Pp. 1578. 32.The Disorders of Cardiac Rhythm.-2nd ed. Vols. 1 & 2. by Leo SèhJ-0’:

Oxford: Blackwell. 1980. Pp. 736. £56.Handbook of Protein SequenceAnalyszs.-2nd ed. By L R. Crof Cbt,,:,’

Wiley. 1980. Pp. 628. 38.Orban’s Oral Hutology & Embryology.-9th ed. S. N. Bhaskar S,, ’

Mosby. London: Y. B. 1980. Pp. 482. £13.50.