1474 mucus. Thus the mucus blanket is kept in a state of elasticity, moving across the cilia with the characteristics of a solid rather than a liquid." These properties of mucus within respiratory secretion make in-vitro study of expectorated sputum difficult. It is a heterogeneous substance with properties of both liquid and solid, and it therefore does not obey Newtonian laws of fluid mechanics. Rheology is the study of flow and deformation of matter. In the case of sputum some of the terms used by biorheologists include viscosity (resistance of flow, though strictly speaking it is not possible to measure viscosity unless a fluid is Newtonian), visco-elasticity or retraction (the property of mucus partially to resume its original shape following shear stress), plasticity (the property of mucus which permits it to be deformed without rupture), stickiness, and the picturesquely termed spinnbarkeit (a term usually applied to cervical mucus and meaning the capacity of mucus to be drawn into threads, as between the opening jaws of forceps). Many of these properties are undoubtedly important clinically, as anyone who has witnessed the desperate attempts of patients with asthma or cystic fibrosis to expectorate stringy sticky mucus will appreciate. Reid and her colleagues have made detailed studies of the properties of mucus;12 2 they have been able to show, for example, that mucus of asthmatic patients contains more glycoprotein than normal, perhaps partly due to simple dehydration, a common problem in breathless, ill patients. A final feature of respiratory mucus, much less studied, is its pH. Throughout the bronchial tree mucus is in equilibrium with carbon dioxide, at pH about 7-4. Buffering systems within the mucus are reasonable effective; the pH value shows diurnal and day-to-day variation of 7-4 to 8-2 in normal subjects.l3 Lower values have been recorded, and asthmatics in particular may have a low pH, even down to 5°3.14 At these low values respiratory epithelium may suffer damage, although cilia themselves seem remarkably tolerant and will continue beating down to pH 5-0 in vitro. Novel experiments by Holma also indicate that viscosity may be dependent upon pH; he showed that gel properties of mucus may be lost above pH 7-5, whilst sputum viscosity may increase with falling pH.lS A further effect of low pH investigated by Holma is the loss of buffering capacity, making asthmatics with their already acidic mucus especially 11. Meyer FA, Silberberg A. Structure and function of mucus. In: Respiratory tract mucus (Ciba Foundation Symposium 54). Amsterdam: Elsevier, 1978: 203-11. 12. Lopez-Vidriero MT, Reid L. Bronchial mucus in health and disease. Br Med Bull 1978; 34: 63-74. 13. Fabricant ND. Significance of the pH of nasal secretions in situ. Arch Otolaryngol 1941; 34: 150-63. 14. Ryley HC, Brogan TD. Variation in the composition of sputum from patients with chronic bronchitis. J Clin Pathol 1968; 49: 625-33. 15. Holma B. Influence of buffer capacity and pH—dependent theological properties of respiratory mucus on health effects due to acidic pollution. Science of the Total Environment 1985; 41: 101-23. susceptible to environmental acid exposure. It is even possible that this is one of the contributing factors to the well known bronchial hyperreactivity experienced by asthmatics when they are exposed to substances such as sulphur dioxide. Gestational Assessment ACCURATE determination of gestational age is fundamental to obstetric care. Prematurity and low birthweight for gestational age are associated with increased perinatal morbidity and mortality; management of these conditions is not without complications, including maternal mortality, and is based on a reliable estimate of gestation. About 25% of patients lack accurate menstrual data, and many of these book after 20 weeks’ gestation. Moreover, uncertain gestation may also be associated with poor perinatal outcome. 3 Ultrasound dating in these situations has transformed modem obstetric practice and is now routine in many centres. The two most widely used ultrasound measurements for gestational assessment are crown- rump length (CRL) in the first trimester4 and biparietal diameter (BPD) in the second.5 Estimates based on CRL measured up to 12 weeks’ gestation are highly accurate, and will predict delivery date to within 5 days ;6 the standard BPD measurement7 is also useful when estimated before 24 weeks’ gestation.8 There are limitations with both these measures, however. Increasing fetal size and flexion towards the end of the first trimester make estimates of CRL more difficult and less accurate, whereas the slower rate of head growth and deformation of head shape make BPD of less use in later pregnancy. Data on BPD were derived from women who were certain of their menstrual dates to calculate a mean and standard deviations; this is not equivalent to a mean and standard deviation of gestational age where the BPD is known, and corrections have been made. Femur length (FL) is also a valuable predictor of gestational age, and almost as reliable as BPD.9 It is 1. MacLennan FM, Thomson MAR, Rankin R, Terry PB, Adey GD. Fatal pulmonary oedema associated with the use of ritodrine in pregnancy. Br J Obstet Gynaecol 1985; 92: 702-05. 2. Grennert L, Persson PH, Gennser G. Acta Obstet Gynecol 1978; 78 (suppl): 5. 3. Hall MH, Carr-Hill RA, Fraser C, Campbell D, Samphier ML. The extent and antecedents of uncertain gestation. Br J Obstet Gynaecol 1985; 92: 445-51. 4. Robinson HP. Sonar measurement of the fetal crown-rump length as a means of assessing maturity in first trimester pregnancy. Br Med J 1973; iv: 28-31. 5. Campbell S, Newman GB. Growth of the fetal biparietal diameter during pregnancy. J Obstet Gynaecol Br Commonw 1971; 78: 513-19. 6. Robinson HP, Fleming JEE. A critical evaluation of sonar crown-rump length measurements. Br J Obstet Gynaecol 1975; 82: 702-10. 7. Hadlock FP, Deter RL, Harrist RB, Park SK. Fetal biparietal diameter: A critical re-evaluation of the relation to menstrual age by means of real-time ultrasound. J Ultrasound Med 1982; 1: 97-104. 8. Bennett MJ. Real-time ultrasound in the second and third trimesters of pregnancy. In: Bennett MJ, Campbell S, eds. Real-time ultrasound in obstetrics. Oxford: Blackwell, 1980: 49-61. 9. O’Brien GD, Queenan JT, Campbell S. Assessment of gestational age in the second trimester by real-time ultrasound measurement of the femur length. Am J Obstet Gynecol 1981; 139: 540-45.
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mucus. Thus the mucus blanket is kept in a state ofelasticity, moving across the cilia with thecharacteristics of a solid rather than a liquid."These properties of mucus within respiratory
secretion make in-vitro study of expectorated sputumdifficult. It is a heterogeneous substance with
properties of both liquid and solid, and it thereforedoes not obey Newtonian laws of fluid mechanics.Rheology is the study of flow and deformation ofmatter. In the case of sputum some of the terms used
by biorheologists include viscosity (resistance of flow,though strictly speaking it is not possible to measureviscosity unless a fluid is Newtonian), visco-elasticityor retraction (the property of mucus partially toresume its original shape following shear stress),plasticity (the property of mucus which permits it tobe deformed without rupture), stickiness, and thepicturesquely termed spinnbarkeit (a term usuallyapplied to cervical mucus and meaning the capacity ofmucus to be drawn into threads, as between theopening jaws of forceps). Many of these properties areundoubtedly important clinically, as anyone who haswitnessed the desperate attempts of patients withasthma or cystic fibrosis to expectorate stringy stickymucus will appreciate. Reid and her colleagues havemade detailed studies of the properties of mucus;12 2
they have been able to show, for example, that mucusof asthmatic patients contains more glycoprotein thannormal, perhaps partly due to simple dehydration, acommon problem in breathless, ill patients. -
A final feature of respiratory mucus, much lessstudied, is its pH. Throughout the bronchial treemucus is in equilibrium with carbon dioxide, at pHabout 7-4. Buffering systems within the mucus arereasonable effective; the pH value shows diurnal andday-to-day variation of 7-4 to 8-2 in normal subjects.l3Lower values have been recorded, and asthmatics inparticular may have a low pH, even down to 5°3.14 Atthese low values respiratory epithelium may sufferdamage, although cilia themselves seem remarkablytolerant and will continue beating down to pH 5-0 invitro. Novel experiments by Holma also indicate thatviscosity may be dependent upon pH; he showed thatgel properties of mucus may be lost above pH 7-5,whilst sputum viscosity may increase with fallingpH.lS A further effect of low pH investigated byHolma is the loss of buffering capacity, makingasthmatics with their already acidic mucus especially
11. Meyer FA, Silberberg A. Structure and function of mucus. In: Respiratory tractmucus (Ciba Foundation Symposium 54). Amsterdam: Elsevier, 1978: 203-11.
12. Lopez-Vidriero MT, Reid L. Bronchial mucus in health and disease. Br Med Bull1978; 34: 63-74.
13. Fabricant ND. Significance of the pH of nasal secretions in situ. Arch Otolaryngol1941; 34: 150-63.
14. Ryley HC, Brogan TD. Variation in the composition of sputum from patients withchronic bronchitis. J Clin Pathol 1968; 49: 625-33.
15. Holma B. Influence of buffer capacity and pH—dependent theological properties ofrespiratory mucus on health effects due to acidic pollution. Science of the TotalEnvironment 1985; 41: 101-23.
susceptible to environmental acid exposure. It is evenpossible that this is one of the contributing factors tothe well known bronchial hyperreactivity experiencedby asthmatics when they are exposed to substancessuch as sulphur dioxide.
Gestational Assessment
ACCURATE determination of gestational age isfundamental to obstetric care. Prematurity and lowbirthweight for gestational age are associated withincreased perinatal morbidity and mortality;management of these conditions is not without
complications, including maternal mortality, and isbased on a reliable estimate of gestation. About 25%of patients lack accurate menstrual data, and many ofthese book after 20 weeks’ gestation. Moreover,uncertain gestation may also be associated with poorperinatal outcome. 3 Ultrasound dating in thesesituations has transformed modem obstetric practiceand is now routine in many centres.The two most widely used ultrasound
measurements for gestational assessment are crown-rump length (CRL) in the first trimester4 and
biparietal diameter (BPD) in the second.5 Estimatesbased on CRL measured up to 12 weeks’ gestation arehighly accurate, and will predict delivery date towithin 5 days ;6 the standard BPD measurement7 isalso useful when estimated before 24 weeks’
gestation.8 There are limitations with both thesemeasures, however. Increasing fetal size and flexiontowards the end of the first trimester make estimates ofCRL more difficult and less accurate, whereas theslower rate of head growth and deformation of headshape make BPD of less use in later pregnancy. Dataon BPD were derived from women who were certainof their menstrual dates to calculate a mean andstandard deviations; this is not equivalent to a meanand standard deviation of gestational age where theBPD is known, and corrections have been made.Femur length (FL) is also a valuable predictor of
gestational age, and almost as reliable as BPD.9 It is
1. MacLennan FM, Thomson MAR, Rankin R, Terry PB, Adey GD. Fatal pulmonaryoedema associated with the use of ritodrine in pregnancy. Br J Obstet Gynaecol1985; 92: 702-05.
2. Grennert L, Persson PH, Gennser G. Acta Obstet Gynecol 1978; 78 (suppl): 5.3. Hall MH, Carr-Hill RA, Fraser C, Campbell D, Samphier ML. The extent and
antecedents of uncertain gestation. Br J Obstet Gynaecol 1985; 92: 445-51.4. Robinson HP. Sonar measurement of the fetal crown-rump length as a means of
assessing maturity in first trimester pregnancy. Br Med J 1973; iv: 28-31.5. Campbell S, Newman GB. Growth of the fetal biparietal diameter during pregnancy. J
Obstet Gynaecol Br Commonw 1971; 78: 513-19.6. Robinson HP, Fleming JEE. A critical evaluation of sonar crown-rump length
re-evaluation of the relation to menstrual age by means of real-time ultrasound. JUltrasound Med 1982; 1: 97-104.
8. Bennett MJ. Real-time ultrasound in the second and third trimesters of pregnancy. In:Bennett MJ, Campbell S, eds. Real-time ultrasound in obstetrics. Oxford:
Blackwell, 1980: 49-61.9. O’Brien GD, Queenan JT, Campbell S. Assessment of gestational age in the second
trimester by real-time ultrasound measurement of the femur length. Am J ObstetGynecol 1981; 139: 540-45.
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useful when it is not possible to measure BPD. Thereis no evidence to justify simple averaging of thegestational assessments from BPD and FLmeasurements as has been suggested.10 Theinterocular distance may also be used to estimate
gestation when the BPD cannot be obtained.ilThe ultimate limitations to the accuracy of
ultrasound methods of assessing gestational age reflectboth biological variation in the size of the conceptusand the properties of ultrasound. Resolution of fetalstructures is determined by the wavelength; a 3-5MHz transducer, as commonly used on real-timemachines, has a resolution limited to 0-44 mm underoptimum conditions. Advances in signal processing,including computed sonography,12 may improve theclarity of the images, but these systems are stillconstrained by the physical principles that governconventional real-time images. Accuracy of theelectronic callipers and the calliper positioningsystems also influence the measurements.
Biological variation and the concept of earlyintrauterine growth failure are controversial issueswith respect to their effects on fetal size in the first halfof pregnancy. Somatic growth is consistent in earlypregnancy, and usually uninfluenced by geographical,ethnic, or socioeconomic factors.13 The most widelyused standards of fetal cephalometry5 excludedmeasurements of babies below the fifth centile for
weight at 40 weeks’ gestation. Primate studies14
suggest that head size is determined early in
pregnancy and therefore estimation of gestationalage of small babies by use of these standards may bemisleading. Occasionally an abnormal rate of headgrowth is seen during the second trimester,is whichcould lead to a large dating error if information ongestational age was taken from a mid-pregnancy BPDmeasurement. It is in the context of theseconsiderations that three new studiesl6-18 on
the accuracy of gestational assessment must beviewed.A study of 1087 pregnancies16 compared the
14. Sabbagha RE, Turner JH, Chez RA. Sonar biparietal diameter growth. Standards inthe rhesus monkey. Am J Obstet Gynecol 1975; 121: 371-74.
15. Bamford FN, Jones VP, Ward BS, Moore WMO. Three case reports of fetal growthretardation in the second trimester. Europ J Obstet Gynecol Reprod Biol 1977; 7:301-05.
16. Yagel S, Adoni A, Oman S, Wax Y, Hochner-Celnikier D. A statistical examination ofthe accuracy of combining femoral length and biparietal diameter as an index offetal gestational age. Br J Obstet Gynaecol 1986; 93: 109-15.
17. Selbing A. Conceptual dating using ultrasonically measured fetal femur length andabdominal diameters in early pregnancy. Br J Obstet Gynaecol 1986; 93: 116-21.
18. Ahmed AG, Klopper A. Estimation of gestational age by last menstrual period, byultrasound scan and SP1 concentration: Comparison with date of delivery. Br JObstet Gynaecol 1986; 93: 122-27.
means of calibration techniques,19 with ultrasoundmeasures as the dependent variables, rather than bystandard regression methods with gestational age asthe dependent variable. The formula devised forgestational age combining BPD and FL had a
precision of ±2-5 weeks up to the 32nd completedweek of pregnancy and 2.75 weeks to the 34th. FLwas also more accurate than BPD for the range of
gestational ages up to 31 weeks. This was a cross-sectional study, excluding babies below the 5th andabove the 95th centiles for weight, but seemingly sexwas not controlled for. Clinical application of thisapproach remains to be tested, but it may prove moreaccurate for gestational assessment in patients whobook very late.
Identification of the distal femoral epiphysealossification centre with high-resolution ultrasoundequipment may be another way of improving theestimation of gestational age .20 Mean age of
appearance of the ossification centre is 32-33 weeks,earlier in the female fetus. Absence of the ossificationcentre suggests a menstrual age less than 34 weeks. Ifthese developments in ultrasound techniques are
applied to the late estimation of gestation, use ofradiographs for this purpose should be eliminated.
Conceptual dating calculated from CRL 6,21 hasbeen used as an accurate reference point17 to assess theprecision of FL and the arithmetic mean of twoabdominal diameters compared with BPD in earlypregnancy, since menstrual data tend to be inaccurate.BPD was found to be more precise in dating up to 130conceptual days than either FL or the mean of twoabdominal diameters. Accurate definition of reference
points for gestational assessment also has implicationsfor studies on birthweights and the pattern of. fetalgrowth. Birthweight-for-gestational-age charts formale and female fetuses were developed in a
Scandinavian population.22 The important findingmade by the Scandinavian workers, in contrast toprevious studies,23 was the linearity of birthweightsfor gestational age without a reduction in growth ratetowards term. Boys were heavier than girls at birth,with greater variation around the regression line infemales. Variation in birthweight about the meandecreased with decreasing length of gestation. Thesefindings suggest that more reliable gestationalassessment will improve understanding of growthpatterns and that birthweight standards for individualpopulations need to be carefully reviewed.
19. Seber GAF. Linear Regression Analysis. New York, John Wiley and Sons, 1977.20. Mahony BS, Calten PW, Filly RA. The distal femoral epiphyseal ossification center in
the assessment of third-trimester menstrual age: Sonographic identification andmeasurement. Radiology 1985; 155: 201-04.
21. Selbing A, Fjallbrant B. Accuracy of conceptual age estimation from fetal crown-rumplength. J Clin Ultrasound 1984; 12: 343-46.
22. Secher NJ, KernHansen P, Lenstrup L, et al. Birthweight for gestational age chartsbased on early ultrasound estimation of gestational age. Br J Obstet Gynaecol 1986;93: 128-34.
23. Gruenwald P. Growth of the human fetus. I. Normal growth and its variation. Am JObstet Gynecol 1966; 94: 1112-19.
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The concept of physiological maturity rather thansimply time in utero is the basis for using theconcentration of placental proteins in the maternalcirculation as a reflection of the stage of gestation.These measures are determined by the functioningmass of trophoblast.24 A study of 62 patients showedthat estimations of delivery date by 0,-specificglycoprotein and by scan were evenly distributedbefore and after the actual delivery date.18 B-specificglycoprotein concentrations are not significantlylowered before 16 weeks’ gestation in pregnancieswhich subsequently abort.26 Further comparisons ofthis approach with ultrasound are indicated.
Routine use of ultrasound dating in early pregnancyhas not changed perinatal mortality significantly. 27 Allpublished studies have had methodologicalproblems.28,29 However, it is impossible to identifyevery patient in whom pregnancy complications maydevelop and in whom management may depend ongestational age. This is the strongest clinical argumentin favour of early ultrasound dating, irrespective of thecertainty of menstrual data.
RECTAL CANCER SHOULD BE TREATED BYEXPERTS
ELSEWHERE in this issue (p 1479), Mr Heald and DrRyall describe consecutive series of 188 patients with rectalcancer; of 115 who had a curative resection, the local tumourrecurrence rate was 3.7% at five years. These figures are thebest ever reported and have been achieved by means of aspecific surgical method which, in essence, incorporatestotal excision of the mesorectum by a meticulous dissectiontechnique. By contrast, traditional methods have relied onblunt dissection and transection of the mesorectum.
Irrespective of the explanation for these excellent results,they suggest that surgical technique itself has more to offerin terms of local cancer control, and therefore patientsurvival, than formerly thought possible. Nevertheless, wemust question whether the results are reproducible byothers, and if so how this outcome can be achieved.
Surgeon-related variability is well recognised in colorectalsurgery,1,2 and it might be suggested that Heald and Ryall’sresults illustrate this fact. Similarly, patient selection mayhave been an important factor, although this is unlikelybecause all patients who had a rectal cancer treated by Healdand Ryall are included in their review.
24. Vermuelen RC, Kurver PH, Arts NF, et al. The relationship between the surface areaof the trophoblast and some placental products. Placenta 1983; 3: 359-66.
25. Westergaard JG, Tersner B, Hau J, Grudzinskas JG. Placental protein measurementsin complicated pregnancies. I. Intrauterine growth retardation. Br J ObstetGynaecol 1984, 91: 1216-23.
26. Jouppila P, Seppala M, Chard T. Pregnancy-specific beta-glycoprotein in
complications of early pregnancy. Lancet 1980; i: 667-68.27. Editorial. Diagnostic ultrasound in pregnancy. Lancet 1984; ii: 201-02.28. Thacker SB. Quality of controlled clinical trials: The case of imaging ultrasound in
obstetrics: A review Br J Obstet Gynaecol 1985, 92: 437-44.29. Lilford RJ, Chard T. Commentary: The routine use of ultrasound. Br J Obstet
Gynaecol 1985; 92: 434-36.1. Ritchie JK. Results of surgery for inflammatory bowel disease: A further survey of one
hospital region. Br Med J 1974, i: 264-68.2. Fielding LP, Stewart-Brown S, Dudley HAF. Surgeon-related variables and the
clinical trial. Lancet 1978; ii: 778-79.
Does the patient population differ from that ordinarilyseen by most general surgeons? There is no evidence tosupport this notion, but there may be some subtledifferences which could be identified by better patientclassification.3,4 Confident interpretation of results will beelusive in the absence of an internationally agreed clinico-pathological staging system for rectal cancer, and it is to behoped that progress in this direction will be swift.
If, as seems likely, the patient population with rectalcancer reported by Heald and Ryall is representative, aspecial interest in this type of surgery coupled with asufficient patient volume to perfect surgical technique maylead to such excellent clinical results. Special interest incolon and rectal surgery has been slow to develop in theUK;s in the USA it is recognised by a specialist "board"examination, although this organisational model may beinappropriate elsewhere. Nevertheless, if the implications ofHeald and Ryall’s results are accepted, as they should be, itwould follow as a first step that general surgeons in districtgeneral hospitals should organise themselves so that each hasa special area of interest (eg, vascular, gut, hepato-biliary-pancreas). Second, and of greater importance, each surgeonshould be prepared to acknowledge the special skills of
colleagues and act in the best interests of the patient. Ofcourse the latter suggestion assumes agreement on thedefinition of problems for which special skill is required.
Perhaps general surgeons should recognise that being ajack-of-all-trades is an outmoded objective and acceptspecialisation within general surgery. There is little doubtthat such an approach would improve patients’ short andlong term well-being, with the added bonus of providing amore cost-effective service.
Whilst much has been written on new methods to
improve patient care, little or nothing has been done toascertain whether the methods are being deployed"Satisfactorily. The time has come for general surgeons to"take it up or give it up", and allow the present level ofknowledge and technical skill to be deployed to the full andnot diluted because of historical generalism or attitudinalrigidity. Not only is this proposition a challenge for surgeonswithin their own institutions, but also for health authorities.If the notion of special interest within general surgerybecomes more widely accepted, it may be that the RoyalColleges should involve themselves in the process because ofits major implications for surgical training.There is need for adjustments to be made in
organisational style of general surgery in the UK; anyproblems engendered as a result should be faced in theknowledge that it will ultimately lead to better patient care.The focus must be on development and consolidation ofareas of clinical interest, rather than on disputes over clinical"turf’ or political conflicts between National Health Serviceand university based surgeons. No one needs reminding ofthe pressures being placed on all health service workers atpresent; this idea could generate an island of progress in anotherwise sinking landscape. The profession should seizethe moment.
3. Zorzitto M, Germanson T, Cummings B, Boyd NF. A method of clinical prognosticstaging for patients with rectal cancer. Dis Col Rectum 1982; 25: 759-65.
4. Chapuis PF, Dent OF, Fisher R, et al. A multivariate analysis of clinical andpathological variables in prognosis after resection of large bowel cancer. Br J Surg1985; 72: 698-702.
