ROLE OF PLASMA EXUDATION IN ASTHMATIC AIRWAYS

1126 At

first,

planned to treat our patients with fish the modified method of Kihara in which a tapeworm by volume of hot water containing cathartic is introduced large into the duodenum by way of a duodenal tube. Before this treatment we wanted to determine the shape, number, and position of the parasites in the intestine by X-ray examination. The most common contrast medium is barium sulphate, but it often causes constipation, so we used gastrografm. This compound is mildly laxative but not toxic and does not affect the following treatment. It also has a we

suitable hyperosmolarity of 1900 mOsm/1. The rapid descent of the parasite after injection of gastrografin was quite unexpected. By this method, descent of the parasite can be observed serially by X-ray examination and the whole live tapeworm with a scolex is expelled. It is easy to determine how much gastrografm should be injected to expel the tapeworm completely since it can be seen

descending. How does gastrografin expel the tapeworm? We first examined the effect of hyperosmolarity. In patient 4 barium sulphate in combination with mannitol, which has the same osmolarity as gastrografin, did not have any effect on the movement of the tapeworm. We then examined whether the surface-active agent ’Polysorbate 80’, which is present in gastrografin, had any effect. In patient 5 a mixture of barium sulphate and polysorbate 80 had some effect in driving the parasite down the intestine but did not lead to its expulsion. Thus, polysorbate 80 seems to have some role in expelling the tapeworm. ’Urografm’ consists of the same contrast medium as gastrografin but does not contain polysorbate 80. In patient 6, this agent did not evoke smooth peristalsis of the intestine or expel the tapeworm. Thus, we speculate that both some physical relation between the parasite and the intestinal mucous membrane and a mechanical action of the intestine, such as peristalsis, are important for expelling the tapeworm. The laxative action of gastrografin may be important, but since this action is very mild, at an appropriate volume gastrografm causes few, if any, adverse effects. There are reports that injection of a large volume of gastrografin causes dehydration,11,12 we observed no dehydration with a volume of 250-500 ml, and we believe that volumes of more than 500 ml are unnecessary. Correspondence should be addressed to K. W., Department of Internal Medicme, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita-city, Osaka, Japan.

Hypothesis ROLE OF PLASMA EXUDATION IN ASTHMATIC AIRWAYS

CARL G. A. PERSSON

Department of Clinical Pharmacology, University Hospital, Lund, Sweden; and Pharmacological Laboratory, AB Draco, Lund

Summary

In normal

asthma,

airway defence and especially in mediators

released

from

inflammatory cells will directly affect the walls of the abundant airway microvessels, making them much more permeable to macromolecules. Through large gaps between actively separated (contracted?) endothelial cells of venules of the tracheobronchial circulation, there is a bulk flow of proteinaceous plasma. The plasma exudate is distributed in the airway wall and it readily passes across an inflamed mucosa into the airway lumen. Plasma in the airway wall causes oedema, which may result in hyperresponsiveness and epithelial shedding. In the lumen its effects are formation of mucus plugs and inhibition of mucociliary transport, and its potent mediators such as the protein products of the kinin, complement, and clotting systems are released. Thus plasma exudation may operate in several aspects of asthmatic diathesis. By positive feedback mechanisms and recruitment and conditioning of inflammatory cells plasma exudate may amplify the inflammatory process. INTRODUCTION

THERE is a resurgence of interest in the inflammatory aspects of asthma, with an emphasis on the eosinophil,l mast cell,2 epithelium,3 platelet,’ macrophage,S and neutrophill and on a putative pro-inflammatory innervationor on select mediators from these sources. Surprisingly, plasma exudation, which may be regarded as a cardinal sign of the inflammatory process has been neglected. I propose that plasma exuded from tracheobronchial microvessels essentially contributes to the physical and pathophysiological aspects of the airway in asthma (figure), and that the venular endothelium of these vessels is an important effector for mediators of asthma and for anti-asthma drugs, because it regulates the leakage of plasma.

REFERENCES 1. Veerannan KM. Antihelmintic effect of yomesan

(niclosamide) in the treatment of tapeworm infection. Antiseptic 1980; 77: 341-43. 2. Yokogawa M, Okura T The treatment of Taema saginata with bitionol. Jap J Parasite 1962; 11: 39-44. 3. Yokota J, Takeuchi K, Onoe S, Kanehira M, Omae N. The treatment of tapeworm infection with atebrin. Therapy 1956; 38: 1389-90. 4. Ulivelli A. Terapia antibiotica della teniasi. Riv Clin Pediatr 1963, 72: 371-83. 5. Yoshida Y, Matsuo K, Ikai T, et al. Treatment of Diphyllobothrium latum and Taenia Antibiotics 1979; 32: 1178-82. saginata infections with aminosidin. Jap J 6. Tongu Y, Aji T, Fukuda T, Itano K, Inatomi S. Ultrastructural changes in

Diphyllobothrium latum from man treated with paromomycin sulfate. Jap J Antibiotics 1982; 35: 2126-30. 7. Damaso DR. Intestinal parasitism, diagnosis and treatment. Am J Trop Med 1932; 12: 477-92 8 Kihara

T, Tsuji O, Kobayashi R, Okazaki S, Kosaki

Part I

K. Studies on large tapeworm. The clinical studies of the beef tapeworm ( Taenia saginata) Jap J

Gastroenterol 1973; 70: 175-88. 9. Kihara T, Kobayashi R, Kosaka K Studies on large tapeworm. Part 2. The epidemiological and clinical studies of the broad tapeworm (Diphyllobothrium) latum ). Jap J Gastroenterol 1973; 70: 189-95. 10. Kihara T, Kobayashi R, Tuji O, Okazaki K Studies on large tapeworm infections in man ( Taenia saginata and Diphyllobothrium latum ) Jap J Gastroenterol 1973; 70: 196-207 11. Harris PD, Neuhauser EBD, Gerth R. The osmotic effect of water soluble contrast media on circulating plasma volume. Am JRoentgenol 1964, 91: 694-98. 12 Kimura K, Isaji S, Iizuka M, et al. Effects of gastrografin enema on the body fluid balance Jap Pediatr Surg 1976; 12: 299-303

TRACHEOBRONCHIAL CAPILLARY-VENULAR PLEXUSES

The trachea and the bronchi possess an extensive and superficial capillary-venular plexuses may play a major part in the inflammatory response of the airways. The hyperaemia of inflammation increases the supply of white cells and platelets, and the vasodilatation causes mucosal swelling.8 Furthermore, the separation (by contraction) of endothelial cells in the postcapillary venules that inflammation causes (figure) results in extensive leakage of plasma, an active process under physiological and pharmacological control.9 Inflammatory extravasation of leucocytes and macromolecular solutes is induced via different mechanisms and can occur separately. White cells seem to have a protein-tight seal during emigration, and mediator-induced leakage of plasma can arise without any cellular escape. 10 Plasma exudate, containing proteinderived mediators, would be important in normal airway defence and would be potentially so in the pathogenesis of asthma (figure). But is plasma exuded in asthmatic airways?

niicrovascularure7

1127

initiating

events

may not be the

characteristic of the disease.

Diagram of possible sequence of events initiated by exposure of airway mucosa and microvessels to inflammatory mediators. Plasma exudate in the lumen contributes to impaired mucociliary transport, mucus plug formation, and small airway narrowing; in the airway wall it contributes to airway hyperresponsiveness, decreased airway compliance, and sloughing of epithelium. Physiologically, plasma exudate is an endless source of potent mediators for important effector cells and may

amplify the inflammatory process in the airways in asthma.

’

century ago that "the vice in asthma consists not in the production of any special irritant, but in the irritability of the part irritated" is relevant to the difficulty we have today in finding a mediator that is peculiar to asthma or a type of cell of the airway in asthma that is abnormally prone to release mediators. The abnormality in asthma should perhaps be sought in events secondary to mediator release. What mechanisms amplify the inflammatory process and transform normal defence actions into a sustained inflammation? ZweifachlO has emphasised that in chronic diseases postcapillary venules may be unusually reactive owing to defects in the collagen and reticular fibres of the perivascular tissue that, together with the endothelial basement membrane, support the vessel. In asthma tracheobronchial microvessels may thus be very sensitive to mediators and have a propensity to sustained leakiness. Such changes would be consistent with observations in asthma of large amounts of plasma proteins in airways.18,19 In normal tissue the vascular leakage response to single mediators lasts less than 15 min and is rapidly tachyphylactic.9 Paf-acether may be an exceptionbecause it induces sustained leakiness (more than 5 h) of guineapig tracheobronchial microvasculature (Erjefalt and

Persson, unpublished). PLASMA EXUDATION IN ASTHMA

Several proposed bronchoconstrictory mediators of asthma (amines, peptides, lipid products, etc) have the additional capacity of increasing microvascular permeability to large molecules and hence inducing plasma exudation.9 Observations on neurogenic vascularll and mucosall2 macromolecular leakage in guineapig airways have attracted interest. However, this mechanism may not operate in non-rodent mammals, and the putative neurotransmitter, substance P, applied on human airway (nasal) mucosa, in doses as high as those that produce systemic cardiovascular effects, seems to be without inflammatory actions.13 Also, acetylcholine, a potent bronchoconstrictor and secretagogue, has no effect on vascular penneability.14 At present it may, therefore, be judged that plasma exudation can be induced in asthma by many cellular and humoral mediators.

Exposure of the airway mucosa to inflammatory mediators will rapidly produce plasma leakage not only into the airway wall but also into the lumen (figure)Y,15 Studies of plasma exudation by analysis of sputum, mucus plugs, and other liquid material sampled selectively from airways show that plasma proteins are present in airways in asthma"" and in

far greater than those found in emphysema," bronchitis, and cystic fibrosis.18 By analogy with events recorded in upper airways the exacerbation of asthma by infection or exposure to allergen and cold dry airI5,20,21 can be expected to be associated with plasma exudation and activation of plasma-derived mediators. Furthermore, clinical improvement is associated with reduced plasma exudation. amounts

AMPLIFYING MECHANISMS

Effector

cells, such

cells, macrophages, or platelets are be the first targets, releasing inflammatory as

mast

eosinophils, epithelial cells, neutrophils,

likely

to

mediators in asthma. Vascular endothelial cells may do too but would not be

so

primary effector cells, at least not to inhaled trigger factors. Thus my hypothesis may not explain the very first events in asthma. On the other hand, these

only distinguishing

Salter’s2z comment from over a

’

Another possibility is that mediators in exuded plasma become particularly active in the airways of asthmatic subjects; in the inflamed airway there are negative surface charges, an abundance of proteases and other prerequisites for an extensive activation of exuded proteins-the kinin, complement, clotting, and other systems. Leaky microvessels are an endless source of mediators and chemoattractant factors, and the variety of precursors and active agents would be sufficient to act on any effector cell in asthma. Several positive feedback mechanisms can be identified, such as effects of plasma-derived mediators on venular endothelium to maintain leakiness and further recruitment and activation of inflammatory cells by factors derived from exuded plasma. Gerberick, Willoughby, and co-workers23 have shown that rabbit alveolar macrophages cannot release reactive oxygen intermediates unless they are conditioned by prolonged exposure to plasma proteins. We may therefore speculate that plasma exudate in the airway results in the conditioning of inflammatory cells, abundant in asthma, to produce and release inflammatory and injurious factors in response to stimuli that otherwise would be harmless to the airways. SMALL OEDEMA: LARGE RESPONSIVENESS

The pathological feactures of asthma are often summarised as oedema, smooth-muscle constriction, epithelial shedding, hypersecretion, and accumulation of eosinophils. Except for oedema these changes have received quantitative support from biopsy and post-mortem examination .3,1.6 It is notable that oedema is mentioned because a small amount of mucosal thickening would not indicate clinically a change in airway calibre; it can, however, be shown (from calculations with Poiseuille’s law) to increase resistance to airflow when there is bronchoconstriction. In contrast to luminal mucus, the oedematous tissue will remain at critical resistance sites. Oedema between the epithelial surface and the bronchial smooth muscle is probably not compressible but may readily be and where this during deformed, happens, bronchoconstriction, there will be large reductions in airway

1128

lumen.24 The relations between mucosal oedema and responsiveness and tendency to closure of airways may now deserve more acceptance as a possible cause of the bronchial hyperresponsiveness that is the clinical hallmark of asthma.25,26 Oedema also causes reduced airway compliance and, perhaps, a decreased threshold for sensory nerve stimulation. 22 OTHER PHYSICAL ASPECTS

The plasma exudate may move rapidly into the lumen of inflamed airway, 12 raising the depth of the periciliary fluid layer and thus inhibiting mucociliary transport.27 In-vitro studies haveshown that mucus and albumin produce complexes that are highly viscous28 and that plasma proteins inhibit the normal swelling process of the mucus gel,29 at luminal concentrations as in asthma, and raise bronchial mucin output.30 Plasma exudation, and fibrin formation, may thus produce the tenacious mucus and the mucus plugs which often are found in the airways after death due to asthma.!6 The presence of extensive deposits of fibrin is the most prominent and striking feature of IgE-dependent late-phase reactions in human skin, whereas cellular infiltration is an inconstant feature.31 Plasma in peripheral airways may destroy surfactant activity and cause small airway collapse.32 Finally, Dunnill’6 has proposed that mucosal oedema and transepithelial passage of plasma exudate cause the sloughing of epithelium characteristic of mild and severe asthma.

some recent observations can be interpreted thus that also xanthines reduce plasma exudation along with symptom reduction in human airways.39 Anti-asthma drugs seem to reduce macromolecular leakage across both endothelial and epithelial barriers.14 Plasma exudation would be of less consequence if the exuded proteins were not activated. Protease inhibitors would then be potentially beneficial in asthma. Such agents have, for other reasons, been examined and found to exert anti-asthma effects.40.4l

an

REFERENCES P. Eosinophil and neutrophil granulocytes in asthma. In. Hogg JC, Ellul-Micallef R, Brattsand R, eds. Glucocorticoids, inflammation and bronchial hyperreactivity. Amsterdam: Excerpta Medica 1984· 21-37. 2. Holgate ST, Hardy C, Robinson C, Agius RM, Howart PH. The mast cell as a primary effector cell in the pathogenesis of asthma. J Allergy Clin Immunol 1986; 77: 274-82. 3. Hogg JC, Walker DC. Pathology of the airway epithelium in asthma Clin Respir

1. Venge

4.

5.

6. 7. 8 9.

10.

11.

THERAPEUTIC IMPLICATIONS

Glucocorticoids, xanthines, sympathomimetic agents, and cromoglycate were used clinically in asthma long before we knew how they worked.633 Indeed we still know too little of their pulmonary pharmacology. Their antiexudative effect may explain why they, and not just any bronchodilator and anti-inflammatory, anti-allergy drug, produce acceptabale clinical responses in asthma. Glucocorticoids have been reported to reduce plasma exudation in inflamed airways. Ryley and Brogan" recorded a relation between reduction of albumin concentration in sputa and steroid therapy and clinical improvement in an asthmatic subject. Keal,34 who looked for effects on secretion in asthma inferred from his observations that the effect of steroid therapy "... lies in the reduction of transudate rather than in any change in the bronchial mucosal gland secretion". These case reports have now been confirmed quantitatively. Methylprednisolone has brought about a large reduction in the sputum concentration of albumin and clinical improvement in patients with bronchitic asthma.35 Stockley and co-workers3637 have shown many aspects of plasma exudation and inhibitory effects of glucocorticoids in chronic bronchitis. Findings in nasal washing experiments lend further support to this action. In allergic subjects prednisolone greatly reduced clinical symptoms and the amount of albumin in washings done during nasal late reaction following challenge with allergen; 15 generation of arachidonate products such as leukotrienes and prostaglandin D was not affected by the steroid treatment. Support for the notion that xanthines, (3z-receptor agonists, and cromoglycate reduce plasma exudation in inflamed airways has been obtained from investigations in animals,9.l4 but also from some unrecognised findings in man. An early report on cromoglycate in asthmatic subjects did, in fact, show that the raised albumin content in sputum returned to control values within two days after starting treatment. 38 Furthermore,

Physiol 1986; 22 (suppl 7)&mid ot; 12-19 Morley J, Page CP, Sanjar S. The platelet m asthma. Lancet 1984; ii. 1142-44. Tonnel AB, Gosset P, Joseph M, Lasalle P, Dessaint JP, Capron A. Alveolar macrophage and its participation m the inflammatory processes of allergic asthma Clin Respir Physiol 1986, 22 (suppl 7): 70-77 Bames PJ. Asthma as an axon reflex Lancet 1986, i. 242-45. Hughes T. Microcirculation of the trachheobronchial tree. Nature 1965; 206: 425-26 Laitinen LA, Robinson NP, Laitinen A, Widdicombe JG. Relationship between tracheal mucosal thickness and vascular resistance in dogs. J Appl Physiol (in press) Persson CGA, Svensjo E Vascular responses and their suppression drugs interfering with venular permeability In Bonta IL, Bray MA, Parnham MJ, eds Handbook of inflammation, Volume 5: The pharmacology of inflammation Amsterdam Elsevier, 1985. 61-81 Zweifach BW Microvascular aspects of tissue injury In Zweifach BW, Grant L, McCluskey RT, eds. The inflammatory process. 2nd ed. New York: Academic Press, 1973: 3-46. Lundberg JM, Brodin E, Sana A Effects and distribution of vagal capsaicin-sensitive substance P neurons with special reference to the trachea and lungs Acta Physiol

Scand 1983, 119: 243-52. 12. Persson CGA, Erjefält I Inflammatory leakage of macromolecules from the vascular compartment into the tracheal lumen. Acta Physiol Scand 1986; 126: 615-16 13. Malm L, Petersson G Tachykinins and nasal secretion. In: Hakanson R, Sundler F, eds. Tachykinin antagonists. Amsterdam: Elsevier, 1985: 199-202 14. Persson CGA, Erjefält I. Non-neural and neural regulation of airway microvascular leakage of macromolecules. In Kaliner MA, Barnes P, eds Neural regulation of the airways in health and disease. Lung biology in health and disease (Lenfant C, ed) New York: Marcel Dekker (in press). 15. Pipkorn U, Proud D, Schleimer RP, et al Effect of systemic glucocorticoid treatment on human nasal mediator release after antigen challenge. J Allergy Clin Immunol 1986; 77 (suppl): 180 16. Dunnill MS The pathology of asthma with special reference to changes in the bronchial mucosa. J Clin Pathol 1960, 13: 27-33 17. Ryley HC, Brogan TD. Variation in the composition of sputum in chronic chest diseases Br J Exp Pathol 1968, 49: 625-33. 18. Brogan TD, Ryley HC, Neale L, Yass J. Soluble proteins of bronchopulmonary secretions from patients with cystic fibrosis asthma and bronchitis. Thorax 1975, 30: 72-79. 19. Guirgis HA, Townley RG. Biochemical study on sputum in asthma and emphysema J Allergy Clin Immunol 1973; 51: 86 20. Rossen RD, Butler WT, Gate TR, Szwed CF, Couch RB Protein composition of nasal secretion during respiratory virus infection Proc Soc Exp Biol Med 1965; 119: 1169-79. 21. Togias AG, Naclerio RM, Proud D, et al Nasal challenge with cold dry air results m release of inflammatory mediators J Clin Invest 1985; 76: 1375-81 22 Salter HH. On asthma. its pathology and treatment. 2nd ed. London Churchill, 1868. 23 Gerberick GF, Jaffe HA, Willoughby JB, Willoughby WF. Relationships between pulmonary inflammation, plasma transudation, and oxygen metabolite secretion by alveolar macrophages. J Immunol 1986; 137: 114-21 24. Hutt G, Wick H Bronchial-lumen und Atemwiderstand. Z Aerosol-Fortch Ther 1956, 5: 131-40. 25. Hargreave FE, Woolcock AJ, eds Airway responsiveness. measurement and interpretation. Mississauga. Astra Canada, 1985: 1-146. 26 Boushey HA, Holzman MJ, Sheller JR, Nadel JA. Bronchial hyperreactivity Am Rev Respir Dis 1980; 121: 389-413 27. Wanner A. Mucociliary function in bronchial asthma In. Weiss EB, Segal MS, Stem M, eds. Bronchial asthma. 2nd ed. Boston. Little, Brown Co, 1985. 270-79 28 Forstner JF, Jabbal I, Findlay BP, Forstner GG Interaction of mucins with calcium, H+ion and albumin. Mod Probl Paediatr 1977, 19: 54-65 29 Aitken ML, Verdugo P Donnan mechanism of mucus hydration effect of soluble proteins. Am Rev Respir Dis 1986; 133: A294 30. Williams IP, Rich B, Richardson PS Action of serum on the output of secretory glycoproeins from human bronchi in vitro Thorax 1983, 38: 682-85. 31. De Shazo RD, Levinson AI, Dvorak HF, Davis RW The late phase skin reaction evidence for activation of the coagulation system in an IgE-dependent reaction in man J Immunol 1979, 122: 692-98 32. Macklem PT, Proctor DF, Hogg J. The stability of peripheral airways. Respir Physiol 1970, 8: 191-203. 33 Persson CGA. On the medical history of xanthines and other remedies for asthma a tribute to HH Salter Thorax 1985; 40: 881-86.

1129

lay-out is the absence of running titles. Although several chapters are largely concerned with the human

Reviews of Books Clinical Trials

Design, Conduct and Analyszs. Curtis L. Meinert and Susan Tonascia. Oxford, New York: Oxford University Press. 1986. Pp 469. 65. THE controlled trial is the heart of modem clinical research, but it is also part of the body of common sense. Take one half of a bouquet of cut flowers and put them into a vase filled with water; put the rest in a similar vase and add a lump of sugar. See which group of flowers lasts longer. That this concept is easier to explain to students than the Fick principle or the sodium pump has led many clinicians to underestimate the complexities and uncertainties of controlled clinical trials; consequently most published trials are far too small to be reliable, too poorly done to inspire confidence, and not well enough described to allow replication. This book, by the editor of Controlled Clinical Trials and his assistant, should do much to improve the quality of clinical trials. It covers with great thoroughness the design, execution, and reporting of multicentre and single-centre uncrossed trials that have a clinical event as endpoint. Sections on randomisation, statistical analysis, special statistical problems (multiple looks, multiple outcomes, multiple comparisons) and stopping rules are authoritative and should be understandable to clinical researchers. The book also offers a brief history of clinical trials, a bibliographic review of all trials published in 1980, and an extensive glossary, and applies the principles it preaches to fourteen North American trials in a massive checklist 20 pages long. It even has a catechism-about 100 questions and answers. Both the authors and the publisher are to be congratulated on the skill with which this complex book was put together. The book’s only failing is that it ignores British and European trials. Once past a polite mention of Bradford Hill in the introduction, the innocent reader would assume that controlled clinical trials were done only in North America. Nevertheless, the main issue, better method, is universal, and Meinert’s book will be the standard for instruction in and evaluation of controlled clinical trials for years to come. Canadian Medical AjoaatKM

PETER MORGAN,

j’ot
Ottawa

Scientific Editor

Physiology and Biochemistry of the Uterus in Pregnancy and Labor The

’

Edited

by Gabor

Huszar. Boca

Raton, Florida: CRC Press. Pp

321.

$126.00.

beautifully produced and comprehensive book, with chapters elucidating various aspects of the eighteen physiology, biochemistry, morphology, and pharmacology of the uterus in pregnancy and labour. It is clearly printed, contains practically no spelling mistakes, and is full of original illustrations. It is mainly a North American product, for of 26 contributors 16 are THIS is

a

review

from the USA and 4 from Canada. Of the remainder, 4 are from Sweden and 1 each from France and Holland. All but one of the chapters provide an introduction listing the subheadings covered and a "conclusions" or summary at the end. A minor criticism of the

uterus, others cite results from so many animal models that the interested reader must continually check the legends of illustrations to identify the species concerned, for it is not always clear in the text. Each chapter provides extensive references, but few after 1983. Perhaps as a result, there is no reference to such topics as the uterine effects of progesterone-inhibiting drugs or to the most recent arguments about the therapeutic value of "tocolytic" drugs in preterm labour. There are also some inconsistencies. In one chapter the initiation of human labour is attributed to increased prostaglandin E2 production by the amnion, while in the next it is ascribed to increased oxytocin receptors in the uterus. Another chapter on the biochemical basis of cervical ripening concludes that collagen breakdown has not been established as the central- cause of the phenomenon, while the two subsequent contributors seem to accept collagenolysis as the basis for the changes. These contradictions are more apparent than real, however, and mainly illustrate a need for continuing research. This important book will be of great value to scientists and clinicians with a special interest in uterine function. Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford OX3 9DU

Radionuclide

A. C. TURNBULL

Imaging in Medicine

Theory and Practice. Peter C. Jackson. London: Farrand Press. £ 18;$28.50.

1986.

Pp

251.

ACCORDING to the preface, this text was designed for use by medical and technical staff, both as an introduction to radionuclide imaging and as an update on new techniques. A "star rating" system is used to indicate whether a section should be considered elementary, intermediate, or advanced. The first four chapters cover, in varied detail, radiation physics and the gamma camera. The text is well and helpfully illustrated, but offers little advantage over other established nuclear medicine texts. The last four chapters, however, on data processing, imaging techniques, and processing, provide an up-to-date review of the state of the art, with excellent sections on single photon emission computed tomographic imaging and image processing. Unfortunately, the book contains too many basic sections to interest the established nuclear medicine practitioner and, in certain sections, too much detail to aid the novice: the material would have been better split into two texts. The star system is generally more irritating than helpful. In addition, the layout of individual chapters often seems illogical, and the positioning of some figures several pages from the text they illustrate may lead to confusion. The absence of a chapter on radiopharmaceuticals is also an important omission from what is otherwise a comprehensive text. Department of Nuclear Medicine, Guy’s Hospital, London SE1 9RT

S. E. M. CLARKE

Endocarditis 34. Keal EE. Biochemistry and rheology of sputum m asthma. Postgrad Med J 1971; 47: 171-77 35 Moretti M, Giannico G, Marchioni CF, Bisetti A. Effects of methylprednisolone on sputum biochemical components in asthmatic bronchitis. Eur J Resp Dis 1984, 65: 365-70. 36. Wiggins J, Elliot JA, Stevenson RD, Stockley RA. Effect of corticosteroids on sputum sol-phase protease inhibitors in chronic obstructive pulmonary disease. Thorax

1982; 37: 652-56. HM, Afford SC, Stockley RA. Inhibitory capacity of alpha1 antitrypsin in lung secretions variability and the effect of drugs. Thorax 1984; 39: 510-16. 38 Heilpem S, Rebuck AS. Effect of disodium cromoglycate (Intal) on sputum protein composition Thorax 1972, 27: 726-28. 39. Nacleno RM, Bartenfelder D, Proud D, et al. Theophylline reduces the response to nasal challenge with allergen. Am J Med 1985, 79 (suppl 6A): 43-47. 40. Budelman H, Burgi H, Regli J. ∈-Aminocaproic acid in asthma. Lancet 1965; ii. 643. 41 Slapke J, Hummel S, Wischnewsky GG, Winkler J Protease inhibitor prevents bronchoconstriction in man Eur JResp Dis 1986, 68: 29-34. 37 Morrison

Medical and Surgical Management. Edited by Donald J. Magilligan, Jr, and Edward L. Quinn. New York: Marcel Dekker. 1986. Pp 269.$55 US and Canada;$66 elsewhere.

THIS is the first volume in a series of monographs entitled Cardiothoracic Surgery. It is expensive and its 34 contributors, nearly half of them from one institution, are all American. A similar format is used for each of the 27 chapters: case presentation, clinical and discussion. Somewhat surprisingly in view of the series title, the first and longest section of the book is concerned with the detailed management of endocarditis caused by specific organisms. The selection reflects experience at the Henry Ford Hospital, Detroit, where clearly endocarditis in drug addicts is common. Most cases of endocarditis in the UK are still caused by

experience,