398
Th results of analysis of the liquor amnii taken at various times in pregnancy indicate that the concentrations of non-hsematin iron and urobilinogen offer a reliable guide to the outcome for the fcetus. Methods of analysis and for obtaining specimens are. described, and it is shown that the iron concentration tends to follow a sigmoid curve. The implications -of this are briefly discussed. Thanks are due to the trustees of the Leverhulme Research Fund and the Royal College of Obstetricians and Gyneecologists for a grant to perform this work ; to the consultant staff at Saint Mary’s Hospitals for referring cases to, the clinic and to all members of the medical and nursing staff for
their cooperation.. REFERENCES
Bevis, D. C. A. (1950) Lancet, ii, 443. Cantarow, A., Stuckert, H., Davis, R. C. (1933) Surg. Gynec. Obstet. 57, 63. Diamond, L. K., Vaughan, V. C., Allen, F. H. jun. (1950) Pediatrics, 6, 630. Flexner, L. B., Gellhorn, A. (1942) Amer. J. Physiol. 136, 757. King, E. J. (1951) Microanalysis in Medical Biochemistry. 2nd ed., London.
Kitzes, G., Elvehjem, C. A., Schuette, H. A. (1944) J. biol. Chem. 155, 653. Kropp, B. (1940) Anat. Rec. 77, 407. London, I. M., West, R., Shemin, D., Rittenberg, D. (1950) J. biol. Chem. 184, 351. Makepeace, A. W., Fremont-Smith, F., Dailey, M. E., Carroll, M. P. (1931) Surg. Gynec. Obstet. 53, 635. Mollison, P. L., Cutbush, M. (1951) Blood, 6, 777. Pommerenke, W. T., Hahn, P. F., Bale, W. F., Balfour, W. M. (1942) Amer. J. Physiol. 137, 164. -
Sandell, E. B. (1950) Colorimetric Determination of Traces of Metals. 2nd ed., New York. Shrewsbury, J. F. D. (1933) Lancet, i, 415. Tankard, A. R., Bagnall, D. J. T., Morris, F. (1934) Analyst, 59, 806. Uranga Imaz, F. A., Gascon, A. (1950) Obstet. Ginec. lat.-amer. 8, 237. Vanotti, A., Delachaux, A. (1949) Iron Metabolism and Its Clinical Significance. London. Winternitz, M. (1926) Klin. Wschr. 5, 988.
TENSION
Baguley Hospital. There had been a history of sudden respiratory distress, attributed to the inhalation of a foreign body. Bronchoscopy at the first hospital had found no foreign body but had given some relief. On admission the child was fairly comfortable but had a loud stridor and some indrawing of the chest wall. He was bronchoscoped under a general anessthetio (Mr. J. S. Glennie), and a piece of rolled-up leaf 1 in. long was removed from th& trachea. Progress.-Next day the child developed an œdema of the glottis as the result of the two bronchoscopies, and at 3 P.M. This produced immediate 9 tracheotomy was necessary. unit at
SUMMARY
PNEUMOTHORAX FOLLOWING TRACHEOTOMY J. F. DARK
Shortly
and the child was comfortable until 8 P.M. after the inner tube had been cleaned at this time the child’s condi. tion suddenly deteriorated ; he became grey-blue and restless, The tube was inspected, and it was not clear whether it was working satisfactorily or not. Oxygen was blown down the tube, the tube was sucked out, and nikethamide was given, but in a few minutes the child was dead. At the time it was thought- that a residual piece of leaf or a piece of blood-clot had been dislodged and had fallen across the carina. Necropsy, however, showed that the airways were patent. Both lungs were completely collapsed, and there were bilateral pneumothoraces. There was severe mediastinal emphysema, with a little surgical emphysema at the neck.
relief,
Case 2.-A girl, aged 5 years, was admitted as an urgent to the ear, nose, and throat ward of the Park Hospital, Davyhulme, with an acute laryngo-tracheo-bronchitis. She had pyrexia, was deeply cyanosed, and was making violent inspiratory efforts with drawing-in of the intercostal spaces, and there was clearly much laryngeal obstruction. A low tracheotomy was immediately done, the child’s colour improved, and breathing became peaceful. Progress.-Three hours later I was asked to see her. She had been quite happy until a short while before, when the breathing had again become difficult, and the colour had deteriorated. On examination she was slate-coloured and making violent inspiratory efforts ; her pulse was rapid and of poor volume, and her skin cold ; there was surgical emphysema of the neck. Oxygen was being administered through a catheter in the tracheotomy tube. At first it was not clear whether the tracheotomy tube was still- in situ, because air still seemed to be going in and out. The patient was certainly very close to death, and after-the experience of case 1 the diagnosis was not difficult. A needle was plunged alternately into each side of the chest, and each time there was a short hiss of air escaping under pressure. The child was taken to the theatre, the tracheotomy wound was laid open, and it was seen that the tube was lying in front of the trachea. It was reintroduced through the tracheal opening. There was little improvement. A needle attached to an artificial pneumothorax machine was plunged into the left chest in the anterior axillary line high up. A positive reading was obtained, and 400 ml. of air was with. drawn. The effect was dramatic. The colour changed toa healthy pink in a few minutes. The process was completed by taking eff 400 ml. of air from the right chest. Radiography showed well the small residual bilateral pneumothoraces and the emphysema of the rnediastinum and neck. With the aid of antibiotics, the child made an uninterrupted case
-
M.B. Manc., F.R.C.S. SENIOR
SURGICAL
REGISTRAR, THORACIC MANCHESTER REGION
SURGICAL
UNIT,
THE fact that mediastinal emphysema and tension may sometimes develop after an incision has been made in the neck is well established. The subject has been admirably reviewed by Reading (1949), who cites two cases following tracheotomy and two following thyroidectomy with associated abductor cord palsy. Champneys (1882), when investigating the relative efficiency of various forms of artificial respiration in stillborn children, noticed that after tracheotomy mediastinal emphysema developed in every case and pneumothoraces in some. Michels (1939) recorded six cases following tracheotomy. Forbes and Salmon (1943) reported on fourteen cases of post-tracheotomy mediastinal emphysema, eight of which developed spontaneous pneumothorax. Barrie (1940) collected four cases of tension pneumothorax seen at necropsy after thyroidectomy. Billimoria ’( 1947) reported a case in which bilateral pneumothoraces occurred during a partial thyroidectomy. This was thought to be due to damage to both pleurae, although no tell-tale hiss was heard. It seems that if there had been a temporary obstruction of the airway used for giving the anæsthetic, these could have occurred through the mechanism as outlined below. No apology is made for reporting yet two more cases ; for the condition is still widely unknown and may account for a high proportion of unexplained deaths following otherwise successful tracheotomy.
pneumothorax
CASE-RECORDS
Case 1:-A healthy male infant, aged 71/2 months, was transferred urgently from another hospital to the thoracic surgical
recovery. DISCUSSION
Reading (1949) explains that, in the presence of a neck involving the pretracheal fascia, such as a tracheo. tomy or thyroidectomy wound, if respiratory obstructian occurs, as when the tracheotomy tube slips out of the previously obstructed air-passage, then, with the ensuing violent inspiratory efforts,, air is sucked into the wound wound
and down into the mediastinum, where it is trapped. More and more air comes in until it breaks out into one or both of the pleural cavities. The site of rupture in the mediastinal pleura has been shown by Ehrenburg (1932) and Macklin (1937) to be either over the thymus anteriorly or between the vertebral column and the oesophagus. Once rupture has occurred, death comes rapidly unless two steps are quickly taken : (1) the patency of the airway must be reinstated, and (2) the air in the pleural cavities must be let off either through cannulae connected to underway!
399
seals, or by an
artificial pneumothorax machine (probably not the best method), or by any means which can be devised with whatever is handy. Air hissing around the tracheotomy tube may give the impression that the tube is still in position ; but blowing oxygen under pressure into the tube (which is the natural impulse) will make the condition worse if the tube is
mal-placed..
If it is realised that the tube has slipped out, and only this is remedied and the pneumothoraces are missed, the patient may die. As Reading (1949) points out, the surest way of forestalling a tragedy is to ensure that the tracheotomy tube will notslip out of position. I wish to thank Mr. A. Graham Bryce and Mr. L. D. Mercer foi permission to record these two cases. :
ADDENDUM
(17-methyl-D-
completing this article I have treated a further case by the method described above, which averted death. Since
Fig. 2—Absorption spectra of colours produced by pregnane-3&agr; : 20&agr;-diol and allopregnane3&bgr; : 20&bgr;-diol ; 0·5 mg. in concentrated sullar to those given phuric acid, I0 ml. The two curves are by the two diols identical below 380 mµ and above 520 mµ.
named above.
EXPERIMENTAL
AS A STANDARD FOR DETERMINATION OF URINARY PREGNANEDIOL W. KLYNE M.A.,
B.Sc. Oxfd, Ph.D. Edin.
SENIOR LECTURER IN BIOCHEMISTRY
POSTGRADUATE MEDICAL SCHOOL OF LONDON
IN the routine determination of urinary pregnanediol by the sulphuric-acid colour reaction it has naturally been the custom to use pregnane-3&agr; : 20&agr;-diol as a standard, since this is the principal constituent of the human urinary diol fraction (Talbot et al. 1941, Guterman
1944,
1945,
Sommerville et al.
1948a and b ; see also Haslewood 1950). Recently it has been shown in this
laboratory (Brooks et al. 1951) that
allopregnane-3&bgr;:20&bgr;diol is
an
important constituent of the diol fraction of Fig. I—Absorptiometer readings
pregnant mares’ urine.
for colours pro. duced by pregnane-3&agr; : 20&agr;-diol and allopregnane3&bgr; : 20&bgr;-diol with I0 ml. of concentrated sulphuric acid.
acid,
colours very simi-
ALLOPREGNANE-3&bgr;: 20&bgr;-DIOL
REGISTRAR IN CHEMICAL PATHOLOGY
3&bgr; : 17&agr;-diol) (Klyne 1950) give,
sulphuric
Barrie, M. J. (1940) Lancet, i, 996. Billimoria, B. R. (1947) Ibid, i, 871. Champneys, F. H. (1882) Med.-chir. Trans. 65, 75. Ehrenburg, G. E. (1932) Amer. Rev. Tuberc. 26, 738. Forbes, G. B., Salmon, G. W. (1943) J. Pediat. 23, 175. Macklin, C. C. (1937) Canad. med. Ass. J. 36, 414. Michels, M. W. (1939) Arch. Otolaryngol. 29, 842. Reading, P. (1949) Guy’s Hosp. Rep. 98, 54.
M.B. Lond.
homoandrostanewith concentrated
REFERENCES
RUTH M. HASLAM
for use in routine determinations of urinary pregnanediol, and saves the labour of making pure pregnane-3&agr; : 20&agr;-diol in quantity. The 3&bgr; : 20&bgr; isomer should not be used in research work on the development of methods for determining pregnanediol or in checking the accuracy of existing procedures—e.g., in recovery experiments. We have also found that allopregnane-3&bgr; : 20&agr;diol and uranediol
We have studied the reaction of this diol with concentrated sulphuric acid, and have found that it gives the same colour as does the human 3&agr; : 20&agr; isomer, both qualitatively and quantitatively. Since allopregnane-3&bgr; : 20&bgr;-diol can easily be obtained by partial synthesis from pregnenolone, which is commercially available, this isomer provides a cheap and convenient standard
20&agr;-diol and allopregnane-3&bgr; : 20&bgr;-diol made to react with sulphuric acid as described by Sommerville et al. (1948a). The pregnane-3&agr; : 20&agr;-diol used was prepared from human pregnancy urine and had a melting-point of 237-238°C. alloPregnane-3&bgr; : 20&bgr;-diol was prepared from pregn-5-en-3&bgr;-ol-20-one acetate by catalytic hydrogenation (Klyne and Barton 1949) and had a melting-point of 194-195°C. Colours produced by different quantities of the two diols were measured with a Hilger Spekker absorptiometer using Ilford Spectrum violet filter no. 601 and a 1 cm. cell. The results for a typical experiment (fig. 1) show that points for quantities of the two compounds up to 0-5 mg. lie The values for very close to the same straight line. the ratio of the weight of pregnanediol in milligrammes to extinction, calculated for the samples represented by the points in fig. 1, were as follows : for the 3&agr; : 20&agr;-diol, 1·18, 1·13, 1·09, 1·08, 1·05 ; and for the allo-3&bgr; : 20&bgr;-diol, 1·18, 1·12, 1·11, 1·09, 1·12. The absorption spectra of the colours from 320 to 700 mµ. were measured on the Beckman spectrophotometer, Model D.U. ; the curves (fig. 2) are identical except for slight differences at about 390 and 430 mµ.
Pregnane-3&agr; :
were
SUMMARY
alloPregnane-3&bgr; : 20&bgr;-diol may conveniently be used instead of pregnane-3&agr; : 20&agr;-diol as a standard in the determination of human urinary pregnanediol by the sulphuric acid colour reaction. We are indebted to N. V. Organon, Oss, Netherlands, for the pregnenolone acetate used, and to Mr. J. P. Newhouse for preparing pregnane-3&agr; : 20&agr;-diol. alloPregnane-3&bgr; : 20&bgr;-diol may be obtained from Organon Laboratories House, Lancaster Place, London, W.C.2.
Ltd., Brettenham
REFERENCES
Brooks, R. V., Klyne, W., Miller, E. (1951) Biochem. J. 49, xl. Guterman, H. S. (1944) J. clin. Endocrinol. 4, 262. (1945) Ibid, 5, 407. Hastewood, G. A. D. (1950) In Emmens, C. W. Hormone Assay. New York ; p. 443. Klyne, W. (1950) Nature, Lond. 166, 559. Barton, D. H. R. (1949) J. Amer. chem. Soc. 71, 1500. Sommerville, I. F., Gough, N., Marrian, G. F. (1948a) J. Endocrinol. —
—
5, 247.
Marrian, G. F., Kellar. R. J. (1948b) Lancet, ii, 89. Talbot, N. B., Berman, R. A., MacLachlan, E. A., Wolfe, J. K. (1941) J. clin. Endocrinol. 1, 668. —