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has shown that prostacyclin generation is powerfullyinfluenced by and may even require a circulatingplasma factors The concentration or activity of thisfactor varies. It may be particularly active in

pregnancy. This could decisively influence thecontinual (as distinct from continuous) generation ofprostacyclin throughout the vascular system.Whichever mechanism may operate in normal

pregnancy-and of course there may be others-a fall inprostacyclin activity could be a link in the chain ofevents leading to pre-eclampsia.21 Measurements ofcirculating prostacyclin metabolites have so far givensomewhat inconsistent results; but prostacyclingeneration in fetal and maternal blood vessels seems tobe reduced or inhibited in toxaemia,26-29 low

prostacyclin levels have been reported in pre-eclampticamniotic fluid,3° and preliminary.clinical trials point tothe possible beneficial effects of prostacyclininfusions.31,32But perhaps the most important clues are still

concealed at the very start of the arachidonic-acidcascade. Almost the only fact known about this is thecritical role of oxygen free radicals. Free radicals are

among the most explosively reactive chemical species;but, with a biological life-span of the order of

microseconds, their study still depends on picking upthe pieces rather than on analysing the explosions.33Some of the immediate products of the free-radicaloxidation of arachidonic acid are rapidly scooped up byspecific enzymes; and it is probably enzymic pathwayswhich lead to the formation of prostaglandins,leukotrienes, and other well-defined families of

compounds. But the immediate products of free-radical reactions also tend to undergo rapid non-enzymic degradation (sometimes involving further free-radical activity); and these non-enzymic derivatives,still incompletely characterised, could both be

biologically active and decisively influence enzyme20. Remuzzi G, Zoja C, Marchesi D, Schieppati A, Mecca G, Misiani R, Donati MB, de

Gaetano G. Plasmatic regulation of vascular prostacyclin in pregnancy. Br Med J1981; 282: 512-14.

21. Ferris TF. Postpartum renal insufficiency. Kidney Int 1978; 14: 383.22. Lewis PJ, Shepherd GL, Ritter J, Chan SMT, Bolton PJ, Jogee M, Myatt L, Elder

MG. Prostacyclin and pre-eclampsia. Lancet 1981; i: 559.25. Mitchell MD. Prostacyclin during human pregnancy and parturition In: Lewis PJ,

O’Grady O, eds. Clinical pharmacology of prostacyclin. New York: Raven Press,1981: 121-29.

24. Ylikorkala O, Viinikka L. Maternal plasma levels of 6-Keto-prostaglandin F. duringpregnancy and puerperium. Prostaglandin Med 1981; 7: 95-99.

25. Ylikorkala O, Kirkinen P, Viinikka L. Maternal plasma prostacyclin concentration inpre-eclampsia and other pregnancy complications. Br J Obstet Gynaecol 1981; 88:968-72.

26. Remuzzi G, Marchesi D, Zoja C, Muratore D, Mecca G, Misiani R, Rossi E, BarbatoM, Capetta P, Donati MB, de Gaetano G. Reduced umbilical and placental vascularprostacyclin in severe pre-eclampsia. Prostaglandins 1980; 20: 105-10.

27. Carreras IO, Breyfen G, Van Houte E, Vermylen J, Van Assche A. Prostacyclin andpre-eclampsia. Lancet 1980; ii: 1374.

28. Downing I, Shepherd GL, Lewis PJ. Reduced prostacyclin production in pre-eclampsia. Lancet 1980; ii: 1374.

29. Stuart MJ, Clark DA, Sunderji SG, Allen JB, Yambo T, Elrad H, Slott JH. Decreasedprostacyclin production: a characteristic of chronic placental insufficiencysyndromes. Lancet 1981; i: 1126-28.

30. Bodzenta A, Thomson GM, Poller L. Prostacyclin activity in amniotic fluid in pre-eclampsia. Lancet 1980; n: 650.

31. Fidler J, Bennett MJ, de Swiet M, Ellis C, Lewis PJ. Treatment of pregnancyhypertension with prostacyclin. Lancet 1980; ii: 31-32.

32. Goodlin RC. Treatment of pregnancy hypertension with prostacyclin. Lancet 1980; ii:310.

33. Dormandy TL. Free radical reactions in biological systems. Ann Roy Coll Surg Engl1980; 62: 188-94.

activity. 34 Prostacyclin synthetase in particular is

powerfully inhibited by several lipid peroxides (e.g.,15-hydroperoxyarachidonic acid) and other non-

enzymic reaction products of hydroxy free radicals ;35and the whole of the arachidonic-acid cascade can beaborted or distorted by free-radical scavengers. 36 ,Fluorescence spectroscopic measurements on plasmaextracts which provide some measure of non-

enzymically generated free-radical products show asteady rise throughout pregnancy, the levels droppingimmediately after labour.3’ There is, moreover, a

correlation between these non-enzymic products andblood-pressure, both rising steeply in some cases ofpre-eclampsia. If normal pregnancy, like normal processesin general, is under the fine control of enzyme systems,abnormal pregnancy, like many other disease states,may reflect the relatively uncontrolled activity of freeradicals.

Echocardiography or Catheterisation?CARDIAC catheterisation has contributed more to

modern cardiology than any other technique. It was thefirst investigation to provide accurate diagnosis ofcardiac disease during life and, combined with

improved surgical and anaesthetic techniques, has ledto modern, safe, cardiac surgery. It enhanced clinicalskills by providing correlations between the physicalsigns and the pathophysiology of heart disease andacted as a standard against which non-invasive

techniques could be assessed. In the past ten years,however, catheterisation has yielded considerable

ground to echocardiography, which is painlessand less costly, and avoids the slight hazard associatedwith the catheter.’ Many people have suggestedthat, eventually, echocardiography will replacecatheterisation? Has that time come? There is no

simple answer. Diagnostic needs differ from conditionto condition and from patient to patient, and cardiaccatheterisation and echocardiography do not alwaysprovide the same type of information. Each has itsadvantages and shortcomings. Neither is of any use inisolation from the clinical picture. This is confirmed bya recent study of echocardiography in a large group ofpatients referred routinely to an echocardiographydepartment.2 The technique proved excellent in itsability to confirm or refute clinically suspecteddiagnoses but of little value when no specificcardiological diagnosis was suspected beforehand.

34. Dormandy TL. Free-radical oxidation and antioxidants. Lancet 1978; i: 247-50.35. Weiss SJ, Turk J, Needleman P. A mechanism for the hydroperoxide-mediated

inactivation of prostacyclin synthetase. Blood 1979; 53: 1191-96.36. Egan RW, Paxton J, Kuehl FA. Mechanism for the irreversible self-deactivation of

prostaglandin synthetase. J Biol Chem 1976; 251: 7329-35.37. Wickens D, Wilkins MH, Lunec J, Ball G, Dormandy TL. Free-radical oxidation

(peroxidation) products in plasma in normal and abnormal pregnancy. Ann ClinBiochem 1981; 18: 158-62.

1. Karnegis JM, Heinz J. The risk of diagnostic cardiovascular catheterisation. Am HeartJ 1979; 97: 291-97.

2. Grimmer SFM, Tindall H, Hill JD. The diagnostic contribution made byechocardiography. Lancet 1982; i: 440 41.

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In congenital heart disease the different types ofinformation provided by catheterisation and

echocardiography are often complementary. Anti-

cipation of the correct diagnosis may allow catheter-isation to be avoided altogether in untreatableconditions such as hypoplastic left heart. More

importantly, it often guides catheterisation; if the

operator knows the diagnosis but catheterises to

confirm specific details, fewer and better angiogramscan be made and the procedure is shortened. This isparticularly important in newborn babies who do badlywith lengthy procedures and large doses of contrastmaterial. M-mode echocardiography helps in the

precatheter assessment of congenital heart disease buttwo-dimensional echocardiography is far superior; itsability to show complex anatomical relationships hasvastly improved non-invasive assessment.3 It providesmultiple "thin sections" of the heart from manydifferent angles. These thin sections overcome theproblems of superimposition of cardiac structures thatarise with angiography, and the number of views is notlimited by the amount of contrast medium that can beused. As a result 2-D echocardiography is often

superior to angiography in displaying complexanatomical relationships-e.g., the region of theatrioventricular junction, the relation of the greatvessels and atrioventricular valves to the ventricles, andthe position of septal defects. This anatomicalinformation, often best provided by echocardiography,may need to be combined with information aboutshunts and pulmonary vascular resistance that can beobtained only from catheterisation, and with finevascular detail that only angiography provides at

present-e.g., the presence or absence of peripheralstenoses in the pulmonary arteries.The information needed in valve disease is often

simpler, and, in the two-thirds of patients in whom anecho tracing of good quality can be obtained,echocardiography and clinical assessment should

provide most of the information required.Catheterisation assesses valve stenosis indirectly frompressure and flow measurements and, although usuallyaccurate, can be misleading.4 M-mode echo-

cardiography can assess stenosis indirectly-e.g., fromspeed of valve motion, slow left ventricular filling inmitral stenosis, or left ventricular hypertrophy inaortic stenosis. In contrast, 2-D echocardiographyassesses stenosis directly and more accurately byshowing a cross-section of the valve orifice*—the onlytechnique that can do this. Angiography remains the

3 Silverman NH, Snider AR. The value of two-dimensional echocardiography in thediagnosis of congenital heart disease. In: Hunter S, Hall R, eds. Echocardiography I.Edinburgh: Churchill Livingstone, 1982.

4. Traill TA, St John Sutton MG, Gibson DG. Mitral stenosis with high left ventriculardiastolic pressure. Br Heart J 1979; 41: 405-11.

5. Hall R, Austin A, Hunter S. M-mode echogram as a means of distinguishing mild andsevere mitral stenosis. Br Heart J 1981; 46: 486-91.

6. Martin RP, Rakowski H, Kleiman JH, Beaver W, London E, Popp RL. Reliability andreproducibility of two dimensional echocardiographic measurement of the stenoticmitral valve orifice area. Am J Cardiol 1979; 43: 560-68.

7. DeMaria AN, Bommen W, Joye J, Lee G, Bouteller J, Mason DT. Value andlimitations of cross-sectional echocardiography of the aortic valve in the diagnosisand quantification of valvular aortic stenosis. Circulation 1980; 62: 304-12.

best method of assessing valvar regurgitation; however,the presence of severe symptoms, typical physicalsigns, and echocardiographic evidence of the effects ofregurgitation on left ventricular function (e.g., volumeoverload) is often sufficient for clinical purposes. Itmust be remembered that an echocardiographicallynormal (M-mode and 2-D) valve is never stenotic butcan be severely regurgitant.What experience is there of using only non-invasive

data, derived from clinical investigation, electro-

cardiogram, chest X-ray, and echocardiogram, for

preoperative assessment? Many centres have longavoided catheterisation in pure mitral stenosis,8although this policy has been questioned,9 and haveused echocardiography to decide whether the valve issufficiently pliable for valvotomy. 10 The value of suchnon-invasive assessment in a wider range of valvedisease has been put to the test in three recent

studies."-’3 In all three, definite recommendations forsurgery based only on non-invasive data were set

against the findings at operation. For patients withmild valvular lesions, such recommendations wereinvariably correct and did not lead to unnecessarysurgery. Two of the studiesll,13 included patients inwhom surgery was not recommended and both showthat non-invasive assessment is very unlikely to misslesions requiring operation-so long as it isremembered that echocardiography may under-estimate the severity of regurgitant lesions," andprovided that catheterisation is used to resolve anydiscrepancy between non-invasive data, symptoms,and physical signs. 13 Decisions about management canbe made on non-invasive grounds alone in about 50%of patients with valve disease11,13 and in 75% of thosewho eventually require valve surgery. 12,13 About a thirdof them will have angina as well as valve disease andrequire coronary angiography. Whether coronarydisease should be sought and operated on in patientswith valve disease but without clinical evidence ofcoronary disease is controversial. 12 Since echo-

cardiography is of little value in the preoperativeassessment of coronary artery disease-the fine detailsof coronary stenoses can be shown only byangiography-the local attitude to this question willultimately determine how often invasive proceduresare thought necessary in valve disease.There are circumstances in which echocardiography

can replace catheterisation; but often catheterisation

8. Motro M, Neufeld HN. Should patients with pure mitral stenosis undergo cardiaccatheterisation? Am J Cardiol 1980; 46: 515-16.

9. Selzer A. Cardiac valve replacement: an unanswered question. Am J Cardiol 1976; 37:322-24.

10. Dernevik L, Brorsson L, Wallentin I, William-Olsson G. Improved results of closedcommissurotomy for mitral stenosis using ultracardiography as selection ground.Acta Med Scand 1981; 210: 283-86.

11. Alpert JS, Sloss LJ, Cohn PF, Grossman W. The diagnostic accuracy of combinedclinical and non-invasive cardiac evaluation: comparison with findings at cardiaccatheterization. Catheterization Cardiovasc Diagnosis 1980; 6: 359-70.

12. St John Sutton MG, St John Sutton M, Oldershaw P, Sacchetti R, Paneth M, LennoxSC, Gibson RV, Gibson DG. Valve replacement without preoperative cardiaccatheterization. N Engl J Med 1981; 305: 1233-38.

13. Hall R, Kadushi OA, Evemy K. Is cardiac catheterisation required routinely beforevalve surgery? Rev Lat Cardiol (in press).

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and echocardiography are complementary. The

frequency with which a completely non-invasiveassessment is adequate depends on the disease inquestion, the technical quality of the echocardiograms,and the attitudes of the cardiologist and cardiac

surgeon.

MECONIUM ILEUS

MECONIUM ileus, the earliest and most severe of theabdominal complications of cystic fibrosis, is not common.Cystic fibrosis occurs in between 1/1150 and 1/2000 1,2 livebirths among white people, and of these babies only 10-15%have meconium ileus, which affects 40-50 babies a year inEngland and Wales. Few paediatric surgical units treat morethan two or three cases a year and this small numbercombined with the early unsatisfactory results of treatment(e.g., only 15% alive after one year3) has made manypaediatricians pessimistic about their management. This wasnot the attitude of Winifred Young, who felt that the

prognosis of babies with meconium ileus should be betterthan that of others born with cystic fibrosis since prophylactictreatment could be started before the onset of lung damage.Her prediction is only now being borne out throughimproved medical management, total parenteral nutrition,non-operative relief of the obstruction by radiocontrastenemas, and improvements in surgical technique. A report4from the Children’s Hospital of Los Angeles, where 31children with meconium ileus were treated in the 18 years1963 to 1980, is encouraging. 3 of the babies were

successfully treated by meglumine diatrizoate enemas, 28required operation, and there were 25 early survivors. Theirsubsequent progress has also been good, with 84% alive at 3months and 71% (20/28) at one year (3 babies were still lessthan one year old at the time of the report). In 1972,McPartlin et al. from London reported a 70% early survivaland Dickson and Mearns6 confirmed these results. Santulli7and Chappell8 have also reported success rates of this order.A ’Gastrografin’ enema9 (meglumine and sodium

diatrizoate) should be tried first in uncomplicated cases and iseffective in up to half. Provided the baby’s condition remainssatisfactory this can be repeated. For complicated cases, thosenot relieved by the enema, and where the diagnosis is in

doubt, operation is still required. The actual technique usedseems less important than the precautions listed by the LosAngeles team-adequate resection of the dilated

hypertrophied segment, complete evacuation-of the bowelcontent proximally and distally, and.care to ensure that the

1. Prosser R, Owen H, Bull F, Parry B, Smerkinich J, Goodwin HA, Dathan J. Screeningfor cystic fibrosis by examination of meconium. Arch Dis Childh 1974; 49: 597-601

2. Stephan U, Busch EW, Kollberg H, Hellsing K. Cystic fibrosis detection by means of atest-strip. Pediatrics 1975; 55: 35-38.

3. Holsclaw DS, Eckstein HB, Nixon HH. Meconium ileus-a 20 year review of 109cases. Am J Dis Child 1965; 109: 101-13.

4. Mabogunje OA, Wang Chun-I, Mahour GH. Improved survival of neonates withmeconium ileus. Arch Surg 1982; 117: 37-40.

5. McPartlin JF, Dickson JAS, Swam VAJ. Meconium ileus. Immediate and long termsurvival Arch Dis Childh 1972; 47: 207-10.

6. Dickson JAS, Mearns MB. Meconium ileus. In: Wilkinson AW, ed. Recent advances inpaediatric surgery. Edinburgh: Churchill Livingstone, 1975: 143-55.

7. Santulli TV Meconium ileus. In Holder TM, Ashcraft KW, eds. Pediatric surgery.Philadelphia: W. B. Saunders, 1980. 356-73.

8. Chappell JS, Management of meconium ileus by resection and end-to-end anastomosis.S Afr Med J 1977; 52: 1093-94.

9. Noblett HR. The treatment of uncomplicated meconium ileus by Gastrografin enema.A preliminary report. J Pediatr Surg 1969; 4: 190.

bowel anastomosed has a good blood supply and is

undamaged by handling. Four different techniques are inuse: resection and double enterostomy, recommended byGross, resection and primary anastomosis, recommendedby Swenson," as used by Chappell and in Los Angeles;4resection and proximal to distal end-to-side anastomosis witha distal enterostomy, recommended by Bishop and Koop;12and the reverse arrangement with a proximal enterostomyand side-to-end anastomosis, recommended by Santulli.13The double enterostomy and Santulli techniques leave aproximal stoma which may require inconveniently earlyclosure. In the past, most surgeons avoided primary ana-stomosis because they feared breakdown in the anastomosisfrom the unsatisfactory nature of the anastomosed gut andbecause a distal obstruction might still be presentpostoperatively. The Bishop/Koop operation carries thetheoretical objection that the safety valve is distal to theanastomosis it is designed to protect, and seems, for no veryobvious reason, to work well for some surgeons and not forothers. The stoma does not cause trouble since it will onlyleak if there is a distal obstruction; closure is a minor

procedure which can be done at any time. Some 40-50% ofcases are complicated (14 out of the 31 in the Los Angelesseries) by perforation, atresias, volvulus, gangrene, andmeconium peritonitis. Where there is much gut damage orloss and healthy ends cannot be obtained without furtherextensive resection, a double enterostomy is probably safestafter the resection in this group. For the others, the bestprocedure is probably the one with which the surgeon ishappiest.

. A corollary to these observations is that, in any case of smallbowel atresia or meconium peritonitis, cystic fibrosis shouldbe excluded by a sweat test. Between 5% and 20%14 of babiesin some series of meconium obstruction prove not to have

cystic fibrosis. The aetiology of these is obscure, but a fulltreatment regimen should be started initially until the

diagnosis of cystic fibrosis has been confirmed or refuted.The standard for results in the treatment ofmeconium ileus

has now been set. Whichever regimen is followed, 90% ofbabies with uncomplicated meconium ileus should survivetheir initial treatment, 70-80% should be alive and well atone year, and more than half should reach their teens inreasonable health.

GIGGLE INCONTINENCE

PHRASES such as "I laughed till I wet myself’ have theirequivalent in many languages. Thus a causal relation betweenlaughing and uncontrolled voiding of urine has long beenaccepted. However, it was not until 1959 that Mac Keith’coined the term "giggle micturition", to separate this form of

10. Gross RE. The surgery of infancy and childhood. Philadelphia: W. B. Saunders, 1953175.

11 Swenson P. Obstruction of the small intestine in the neonatal period. In: Swenson 0,ed. Pediatric surgery, 1st ed. New York: Appleton-Century-Crofts, 1958: 319.

12. Bishop HC, Koop CE. Management of meconium ileus: resection, Roux-en-Yanastomosis and ileostomy, irrigation with pancreatic enzymes. Ann Surg 1957;145: 410.

13. Santulli TV. Meconium ileus. In: Mustard WT, Ravitch MM, Snyder WH, Welch KJ,Benson CD, eds. Pediatric surgery, 2nd ed. Chicago: Year Book Medical

Publishers, 1969: 851.14. Rickham PP, Boeckman CR. Neonatal meconium obstruction in the absence of

mucoviscidosis. Am J.Surg 1965; 109: 173.1. Mac Keith RC. Micturition induced by giggling? cataplexy. Arch Dis Childh 1959; 34:

358.