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airways.’ This is not limited to the airways since localapplication of cholinergic agonists induces greater sweatingand pupillary responses in asthmatics than in normal

controls. 23Several lines of evidence suggest that alpha-adrenergic

responsiveness is increased in asthmatics. Alpha-adrenergicstimulation has no effect on normal human airways in vitro,but in the presence of histamine or in diseased airways itproduces contraction.24 Inhaled alpha-adrenergic agonistscause bronchoconstriction (in the presence of beta-blockade)in asthmatics but not in normal subjects.25,26 In an

experimental model of asthma, and in chronic airwayobstruction in man, an increase in pulmonary alpha-receptordensity was found.27,28 The alpha-adrenergichyperresponsiveness seems to be generalised since, as withcholinergics, asthmatics have exaggerated pupillary andcutaneous vascular responses to locally applied alpha-agonists.29

’

In non-asthmatic atopic subjects, with or without rhinitis,beta-adrenergic responsiveness is reduced and cholinergicresponsiveness increased to the same extent as in asthmaticsubjects, but there is no similar increase in alpha-adrenergicresponsiveness.5 This suggests that reduced beta-adrenergicand increased cholinergic responses may be related to atopy,but that asthmatics in addition have an increase in alpha-adrenergic responsiveness.The interrelations between various components of theautonomic nervous system are complex. Cholinergic tonemay be modulated by beta-adrenergic stimulation at airwayganglia or at postganglionic level." Cholinergic stimulationmay reduce adrenergic neurotransmission31,32 and may alsoincrease alpha-adrenergic responsiveness of the airways.33Beta-adrenergic stimulation, while reducing beta-receptordensity, may simultaneously increase alpha-receptordensity. 34 An abnormality of one component of theautonomic nervous system may therefore cause secondaryabnormalities in other components. The clinical relevance ofthese abnormalities remains to be determined. That theimbalance in autonomic control is the primary defect inasthma seems unlikely; administration of beta-blockers tonormal subjects does not make them asthmatic. More likely,these autonomic abnormalities in asthma are secondary tosome more fundamental defect, such as increased secretion of

22. Kaliner M. The cholinergic nervous system and immediate hypersensitivity. I. Eccrinesweat responses in allergic patients. J Allergy Clin Immunol 1976, 58: 308-15.

23. Smith LJ, Shelhamer JH, Kaliner M. Cholinergic nervous system and immediatehypersensitivity. II. An analysis of pupillary responses. J Allergy Clin Immunol1980; 66: 374-78.

24. Kneussl MP, Richardson JB. Alpha-adrenergic receptors in human and canine trachealand bronchial smooth muscle. J Appl Physiol 1978; 45: 307-11.

25. Patel KR, Kerr JW. The airways response to phenylephrine after blockade of alpha andbeta receptors in extrinsic bronchial asthma. Clin Allergy 1973; 3: 439-48.

26. Snashall PD, Boother FA, Sterling GA The effect of alpha-adrenoceptors studied byradioligand binding. Clin Sci Mol Med 1978; 54: 283-89

27. Barnes PJ, Dollery CT, MacDermot J. Increased pulmonary alpha-adrenergic andreduced beta-adrenergic receptors in experimental asthma. Nature 1980; 285:569-71.

28 Barnes PJ, Karliner JS, Dollery CT. Human lung adrenoceptors studied by radioligandbinding. Clin Sci 1980; 58: 457-61.

29. Henderson WR, Shelhamer JH, Reingold DB, Smith LJ, Evans R III, Kaliner M.Alpha-adrenergic hyper-responsiveness in asthma. N Engl J Med 1979; 300:642-47.

30. Vermeire PA, Vanhoutte PM. Inhibitory effects of catecholamines in isolated caninebronchial smooth muscle J Appl Physiol 1979; 46: 787-91

31. Vanhoutte PM. Cholinergic inhibition of adrenergic transmission. Fed Proc 1977; 36:2444-49.

32. Russell JA, Bartlett S. Adrenergic neurotransmission in the airways: inhibition byacetylcholine. J Appl Physiol 1981; 51: 376-83.

33. Ohno Y, Watanabe M, Kasuya Y. Manifestation of latent alpha-excitatory response inthe canine tracheal smooth muscle preparation Relation to basal tone. Arch Int

Pharmocodyn 1981; 251: 205-1634. Maggi A, U’Pritchard DC, Enva SJ. Beta-adrenergic regulation of &agr;2-adrenergic

receptors in the central nervous system. Science 1980; 207: 645-47.

mast- cell mediators, which then leads to changes in

autonomic neurotransmission, in autonomic receptors, or ineffector mechanisms.

INDUCTION OF LABOUR FOR POSTMATURITY

THE postmature fetus is exposed to many dangers.Increasing growth and inefficient uterine action may causedelay in labour and lead to traumatic delivery of the head,breech, or shoulders. About 40% of postmature fetuses opentheir bowels before delivery. 1,2 Hypoxic fetal distress must beexcluded; and, even if this is done, the risk of meconiuminhalation remains. Diminished liquor volume increases therisk of cord compression.3 Since third-trimester liquor hasantibacterial properties in healthy women,4 the

oligohydramnios of the postmaturity syndrome may inaddition enhance the risk ofchorioamnionitis. Even if there isno general tendency to placental insufficiency and fetal

suboxygenation,5,6 fetal death before the onset of labour andfetal distress during labour are not uncommon; and fetaldeath in particular is difficult to anticipate even with moderncardiotocography.3,7 The anxiety which may develop in themother (and be fuelled by the concern of her family) when herbaby’s "time to be born" is past could adversely affect theuteroplacental circulation.8,9 And the more mature the fetusthe less is its ability to withstand hypoxia.10 Small wonderthen that even in modern times perinatal mortality andserious morbidity rates as high as 13% are still being reportedin association with prolonged pregnancy. Can these hazardsand their associated mortality and morbidity be prevented bytimely induction of labour?

In a series of 2000 patients reported by Noble" last year,labour was induced routinely in 350 whose pregnancies werecontinuing at 41 weeks. Maturity had been confirmed byearly ultrasound at about 18 weeks. Labour was induced withprostaglandin E2 vaginal pessaries, followed a day later bysurgical rupture of the forewaters for the 40% of patients whowere not in labour. There were no perinatal deaths, noproblems with respiratory distress of the newborn, and noincrease in the incidence of neonatal jaundice in the 350patients whose labours were induced routinely at 41 weeks.Furthermore the caesarean-section rate in these patients wasonly 5 - 7% and none of these was for failed induction.In a series of 2000 patients now reported by Gibb et al.,12

"certain postmaturity" was diagnosed at 42 weeks in 81. Ofthese 81 patients 30 had labour induced while 51 had thrice-weekly cardiotocography and other tests until labour began

1. Miller FC, Read JA. Intrapartum assessment of the postdate fetus. Am J Obstet Gynecol1981; 141: 516-20.

2. Knox EG, Huddlestone JF, Flowers CE. Management of prolonged pregnancy;Results of prospective randomized trial. Am J Obstet Gynecol 1979; 134: 376-81.

3. Miyazaki FS, Miyazaki BA. False reactive nonstress tests in postterm pregnancies. AmJ Obstet Gynecol 1981, 140: 269-76.

4. Appelbaum PC, Holloway Y, Ross SM, Dhupelia I. The effect of amniotic fluid onbacterial growth in three population groups. Am J Obstet Gynecol 1977; 128:868-71.

5. Bancroft-Livingston G, Neill DW. Studies in prolonged pregnancy. I. Cord blood

oxygen levels at delivery. J Obstet Gynaecol Br Emp 1957; 64: 498-503.6. Mathews DD. The oxygen supply of the postmature foetus before the onset of labour. J

Obstet Gynaecol Br Commonw 1967; 74: 523-27.7. Eaton CJ. Discussion of paper by Knox et al.2 Am J Obstet Gynecol 1979; 134: 383.8. Rosenfeld CR, Barton MD, Meschia G. Effects ofepinephrine on distribution of blood

flow in the pregnant ewe. Am J Obstet Gynecol 1976; 124: 156-63.9. Morishima HO, Pederson H, Finster M. The influence of maternal psychological

stress on the fetus. Am J Obstet Gynecol 1978; 131: 286-90.10. Shelley HJ The metabolic response of the fetus to hypoxia. J Obstet Gynaecol Br

Commonw 1969, 76: 1-15.11. Noble AD. Prevention of postmaturity by routine induction of labour at forty-one

weeks maturity. Obstet Gynaecol 1981; 2: 88-8912 Gibb DMF, Cardozo LD, Studd JWW, Cooper DJ. Br J Obstet Gynaecol 1982; 89:

292-95.

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spontaneously in all patients before 44 weeks. The treatmentgiven depended on which of two consultants the patienthappened to have been booked under. Again there were noperinatal deaths but significantly more births after inducedlabour were associated with one-minute Apgar scores of lessthan 5. 8 patients in the induction group were delivered bycaesarean section as opposed to only 5 in the larger non-induction group. This difference is statistically significant(p<0 05) and was even more striking when induced and non-induced labours were compared in patients with "uncertainpostmaturity". Gibb and co-workers conclude that

uncomplicated postmaturity is not an indication forinduction oflabour because it seems to increase the caesarean-section rate without improving the outlook for the baby.While these two British studies, taken at face value (only

one was controlled and that not randomised), seem to point toopposite conclusions regarding the value of induction oflabour in postmaturity, this is not necessarily so. By inducinglabour routinely at 41 weeks, Noble sought to avoid

postmaturity and its problems. The weakness of the morestandard British practice of inducing labour at 42 weeks, as inthe Gibb study, is that it allows the postmaturity to developand then compounds the hazards with those associated withinduction of labour and oxytocin infusion. Those thinking offollowing Noble’s example should bear in mind that all

patients had the maturity of their pregnancies confirmed byearly ultrasonic scan. Those considering adopting a

conservative approach to postmaturity should reflect thatonly 51 patients in which the diagnosis was certain in theGibb study were so managed, and prepare themselves for theoccasional harrowing intrauterine fetal death before the onsetof spontaneous labour. In neither report is there anyindication of the reaction of patients to elective induction oflabour or conservative management.

MYSTERIOUS PLEURAL EFFUSIONS

THE incidence of pleural effusions is hard to estimate. Onesurvey showed a prevalence -of around 4% among 16 388chest-clinic attenders.’ Common causes include underlyingbronchogenic carcinoma or pneumonia, pulmonary emboluswith infarction, and heart failure. Sometimes the effusionarises without evidence of lung involvement. Tuberculosis isan important cause of effusions and less than 30 years ago"unexplained’ effusions in young people were almost alwaysdue to tuberculosis. Of 141 United States military personnelwith isolated pleural effusions, three-quarters of those under25 years old and half of those over 25 years old acquired activepulmonary tuberculosis within 5 years of the initial effusion,2 2Other causes of mysterious pleural effusions are viralinfections and connective-tissue diseases. In those due to viralinfections the onset is sudden, with fever. Proof of the viralaetiology is seldom obtained, except when an epidemic isclosely investigated. 3 As to connective-tissue disease,pleurisy and pleural effusions, sometimes large, are a

recognised feature of systemic lupus erythematosus.4 Walkerand Wright5 studied 516 patients with rheumatoid arthritisand 301 reference patients with degenerative joint disease:

1. Sochocky S. Pleural effusion: a review of 632 casses. Br J Clin Pract 1966; 20: 619-27.2. Roper WH, Waring JJ. Primary serofibrinous pleural effusion in military personnel.

Am Rev Tuberc 1955; 71: 616-34.3. Gaensler EA. "Idiopathic" pleural effusion. N Engl J Med 1970; 283: 816-17.4. Hughes GVR. Connective tissue diseases. Oxford: Blackwell, 1977; 25.5. Walker WC, Wright V Rheumatoid pleuritis. Ann Rheum Dis 1967; 26: 467-74.

there were 17 unexplained effusions among the rheumatoidarthritis patients and only 1 among the referents. Pleural

biopsy was said to be useful diagnostically in 40% of therheumatoid effusions.

Among the more recently recognised causes of benignpleural effusion is asbestos. Some of the most familiarfeatures of asbestos-related disease are encountered in the

pleura-plaques, diffuse thickening, calcification,mesothelioma6-and the past 20 years have seen numerousreports of pleurisy and effusions after asbestos exposure,sometimes bloodstained and often recurrent and bilateral,and sometimes without evidence of pulmonary fibrosis.7-11Progression to diffuse pleural thickening and mesotheliomahas been recorded.7,8 Epler and co-workers 12 now report aninquiry into pleural effusions among 1135 asbestos-exposedworkers and 717 non-exposed university employees. In theexposed population they found 34 benign pleural effusions;in the control population they found none. (Effusions weredesignated benign if no malignant tumour developed within 3years.) The incidence of pleural effusion increased from 0.7 7to 9-2 per 1000 person-years with increasing degrees ofasbestos exposure. The latent period between first asbestosexposure and pleural effusion is shorter than for otherasbestos-related conditions-usually less than 20 years andsometimes less than 10 years. 12,13 In one study pleuraleffusion was the most common asbestos-related abnormalitywithin 20 years of first exposure. 12 Many of the effusions aresymptomless and transient, so the true incidence is likely tobe higher than that revealed by prevalence surveys. 12,13 Somecases present with fever and malaise, mimicking a viralillness.13 Diagnosis is based on a history of exposure andexclusion of other causes of effusion. Pleural biopsyspecimens, especially when taken with a needle, tend to beuninformative. 14Benign effusions, particularly when large, may be hard to

differentiate from mesotheliomas. A comparison of 31 benigneffusions and 24 due to mesothelioma showed that pain orblood in the effusion were not more common withmesotheliomas but large or recurrent effusions were morelikely to be due to mesothelioma. 15 Several groups havereported follow-up in men with benign asbestos pleuraleffusions. Of 13 Australians,16 4 went on to mesotheliomaand 2 to lung cancer; asbestosis was present or developed in 6.A more recent Australian study of 22 men with benigneffusions showed no malignant tumours after up to 17

years.13 Of 34 followed for up to 27 years, 18 had residualdiffuse pleural thickening, 8 had recurrent effusions, and 1had mesothelioma (after 6 years).12 The numbers were toosmall and the follow-up too short for assessment of the riskthat lung cancer or mesothelioma will develop after benigneffusion. When a mesothelioma follows after some years, it

may be unrelated to the original effusion; or a precursor or aslow-growing tumour may have been present all the time. 146. Parkes WR. Occupational lung disorders, 2nd ed. London: Butterworths, 1981.7. Eisenstadt HB. Pleural asbestosis. Am Pract 1962, 13: 573-78.8. Eisenstadt HB. Benign asbestos pleurisy JAMA 1965; 192: 419-21.9. Smyth NPD, Goodman G, Basu AP, Keshishian JM. Pulmonary asbestosis Chest

1971; 60: 270-73.10. Sluis-Cremer GK, Webster I. Acute pleurisy in asbestos exposed persons. Environ Res

1972; 5: 380-92.11. Nyriredy G. Benign asbestos-induced pleurisy. Prax Pneumol 1975; 29: 166-69.12. Epler GR, McLoud TC, Gaensler EA. Prevalence and incidence of benign asbestos

pleural effusion in a working population. JAMA 1982, 247: 617-22.13. Robinson BWS, Musk AW. Benign asbestos pleural effusion: diagnosis and course.

Thorax 1981; 36: 896-900.14. Gaensler EA, Kaplan AI Asbestos pleural effusion. Ann Intern Med 1971; 74: 178-91.15. Sheers G. Pleural effusions in men exposed to asbestos Communication to

Westcountry Physicians’ Club, 1970.16. Elder JL. A study of 16 cases of pleurisy with effusions in ex-miners from Wittenoon

Gorge. Aust NZ Med J 1972; 2: 328-29.