DR. E. HUGHES: CRANIOTABES OF THE FŒTUS AND INFANT. 1045

.experiments of Neuschlosz,40 who found that an emulsion of lecithin in water possesses a surface CRANIOTABES OF THE FŒTUS AND tension dependent on the amount of Ca present. INFANT. Too much or too little Ca had the same effect. In the therapeutic application of lime salts one also BY EDMUND HUGHES, M.R.C.S., L.R.C.P. LOND often notices opposite effects according to the amount used. IN a previous paper 1 I recorded some results of a To return for a moment t,o what Prof. Bayliss has clinical inquiry into this subject. The account then .called the " Clowes’s effect," it would seem that the given was composed under the combined disadvantages is view of the American author strongly supported of military service and paper shortage ; and this was by our experiments on the stereo-isomeric sugars. unfortunate, because the contentious nature of We have seen that pores are left between the oil- certain of the findings called for their rather full that ,drops, and it is obvious these pores, because presentment. I shall therefore make no apology they are subjected to the surface tension at the for re-stating these findings in somewhat more boundary, assume varying shapes. Now pores of a adequate form. could allow a con- definite shape sugars of definite Broadly, the position then reached was that the figuration-e.g., lævulose-to pass through, while recognised " craniotabes " arising during the first holding back sugars-e.g., glucose--of another con- few months of infancy is in many, and probably in be inclined figuration. One might to explain this most, cases only a fresh manifestation of a state of phenomenon by the aid of differences in viscosity or craniatrophy already existing in later fcetal life, But we surface tension. have found with Miss S. C. This foetal craniatrophy, having no physical differ- Hamburger that these physical constants are the ences from the later form, and occurring predominantly same for lævulose and for glucose. How can one in the same individuals, was therefore held to deserve explain this separation of glucose from lævulose, the same title. Verification of this finding would therefore, other than by supposing that the shape of entail a re-scrutiny of the common belief that cranio- the ultra-microscopic pores in the sieve plays a tabes is a sign of rickets. A simpler solution of the decisive part ? Our experiments thus lend support difficulty would be to infer the causality of syphilis. to Clowes’s theory, and vice versa the mechanism of But the only definite contribution to the problem - specific permeability has become clearer. of causality I was able to make consisted of some fresh Finally, it may be said that the conditions shown evidence tending to rule out syphilis as an acting or in our sketch by the portion below the line do not, proximate cause. The evidence given was, I think, as a rule, occur in physiological circumstances. In sufficient for that purpose ; and it must be remem- fact we know that, as a rute, all the cells of the body bered that observation alone, though powerless to are permeable to water. But there are exceptions. decide what is causal, can often determine what is not. When blood is diluted with a great deal of water I will now go over the previous findings, incor- most of the red corpuscles in absorbing water loose porating such fresh material as has since been obtained. their colouring matter and the mixture has become The total case-material is 154. But after I often saw transparent. centrifugalising of the Skull. a deposit which examined by the microscope proved Immaturity to consist of red corpuscles. These cells must have In connexion with yielding areas in the skull at been impermeable to water. Red corpuscles treated birth, the problem was early raised in course of this as to characters kind in with cobra venom are also impermeable to water. inquiry what of this the can imma- and the same is true of the eggs of sea-urchins.41 newborn skull be legitimately ascribed to When put in distilled water the latter does not enter turity. To determine this point, a parallel study was made on some hundreds of neo-natal the eggs, as Ralph Lillie has pointed out, but on living crania at various of and of adding some Ca-ions their impermeability to water stages development, is lost. stillborn and non-viable crania, in situ and detached.* References. Seeing that in all my cases of foetal craniotabes the bones were and that all were born 1. Hamburger : Zeitschr. f. Biol., 1889, p. 414. parietal attacked, 2. Hamburger : Koninkl. Akad. v. Wetensch. te Amsterdam, at or near term, interest here centres on the condition meeting of Dec. 29th, 1883. of the parietal at and near the end of the foetal 3. Hugo de Vries : Koninkl. Akad. v. Wetensch. te Amster- The result of makes it clear that the dam, meeting of Oct. 27th, 1882. period. study 4. Van’t Hoff: Wie die Theorie der Lösungen Entstand, condition I call foetal craniotabes and the condition Berichte d. Deutsch. Chem., Gesellsch., xxvi., 6, 1894. of the parietal due to immaturity are entirely distinct. 5. Arrhenius : Zeitschr. f. Physik., Chemie, i., 63, 1887. In the first there is of the 6. Hamburger: Zentralbl. f. Physiol., June 17th, 1893, discontinuity bone-forming Jan. 27th, and Feb. 24th, 1894. spicules-a true atrophy in some part of their course- 7. Hedin: Skandinav. Arch. f. Physiol., 1892, pp. 134 and 360. 8. Overton: Studien über die Narkose, Jena, 1901. * For the great majority (about 130) of these latter my thanks 9. Hamburger: Zeitschr. f. Biol., xxviii., 1892, 405. are due to Prof. J. M. Beattie, who kindly placed at my disposal 10. Zuntz : Dissert. Bonn, 1868 ; Loewy und Zuntz : the stillborn material brought to the Liverpool City Laboratory. Pflüger’s Arch., lviii., 1894, p. 511. This material has also furnished several morbid specimens. 11. V. Korányi: Zeitschr. f. Klin. Med., xxxiii., 1897, p. 1; xxxiv., 1898, p. 1. 12. Yandell Henderson : Jour. of Biol. Chem., xxxiii., 333, 1918. 13. Arch. f. Anat. u. 1891, Hamburger: Physiol., p. 31. Brit. Med. Jour., March 1919 ; Proc., vol. xxii., No. 4. 14. Hamburger : Osmot. Druck u. Ionenlehre, Bd. iii., p. 53. 8th, pp. 351 and 360, 1919 : and Alons: Biochem, 15. Demoor : Bull. de l’Acad. Roy. d. Belgique, N. 12, p. 857, Hamburger 1906. Zeitschr., xciv., p. 129, 1919 ; Brinkman : Quarterly Jour. of Physiol., p. 2, 1919. 16. Hamburger : Wiener Klin. Wochenschr., N. 14 u. 15, Exp. xii., 1916 ; de Boer : Jour. of li., 1917. 28. Bahlmann : Dissert, Utrecht, 1920. Physiol., 211, 29. Rona u. Takahashi : Biochem. 1913. 17. Hamburger and Bubanovic : Arch. Internat. d. Physiol., Zeitsehr., xlix., 370, x., 1910. 30. Sörensen: See Neuberg, Der Harn II., p. 1396, 1911. 31. Brinkman: Biochem. Zeitschr., xcv., p. 101, 1919. 18. Kœppe : Pflüger’s Arch., lxvii., 189, 1897. 32. Brinkman and V. Creveld : Yet to 19. : Zeitschr. f. 405. appear. Hamburger Biol., 1891, p. 33. Brinkman and V. Dam : Koninkl. Acad. v. Wetensch. te 20. Girard: C. r. de l’Acad. d. Sciences, cxlviii., p. 1047, Amsterdam, meeting of Dec. 18th, 1920. 1909; clxx., p. 821, 1920. Not 21. Lazarus Barlow : Jour. of 1895. 34. yet published. Physiol., xix., 140, 35. V. Creveld and Brinkman : Koninkl. Acad. v. Wetensch. 22. Gryns: Koninkl. Akad. v. Wetensch. te Amsterdam, meeting of Feb. 1894 ; 1896. te Amsterdam, meeting of Dec. 18th, 1920. 24th, Pflüger’s Arch., lxiii., 86, 36. Brinkman and V. Dam : Arch. Internat. de Physiol., xv., 23. Nagel’s Handbuch II., p. 744, 1907. 24. Hamburger : Physik.-chem. Untersuchungen über Phago- p. 105, 1919. zyten, Wiesbaden, 1912. 37. Brinkman : Quarterly Jour. of Exp. Physiol., xii., p. 2, 25. Snapper : Biochem. Zeitschr., li., p. 62, 1913. 1919. 38. Clowes : Jour. of Physic. Chem., xx., p. 407. 26. Hamburger : Arch. (f. Anat. u.) Physiol. i., p. 317, 1898. 27. and Brinkman : of the Kononkl. 39. Bancroft: Jour. of Physic. Chem., xvii., p. 501. Hamburger Proceedings 40. Neuschlosz : 17, 1920. Akad. v. Wetensch. te Amsterdam, vol. xix., No. 8, pp. 989, Pflüger’s Arch., clxxxi., 41. Lillie : Amer. Jour. of x., p. 997, 1917 ; Proc., vol. xx., No. 5, p. 668, 1918 ; Biochem. Physiol., 419, 1904 ; xvii., vol. No. 89, 1906 ; xxi., 200, 1908 ; xxiv., 459, 1909 ; xxvii., 289, 1911. Zeitschr., lxxxviii., p. 97, 1918 ; Proc., xxi., 4, p. 548, Full about until 1901 in 1918; Biochem. Zeitschr., xciv., p. 131, 1919 ; Hamburger: particulars permeability Hamburger : Osmotischer Druck u. Ionenlehre, 1901-04 (Bergmann, Wiesbaden). 1046 DR. E. HUGHES: CRANIOTABES OF THE FŒTUS AND INFANT. together, sometimes, with attempts at repair; in fcetal with the infantile form, and this will now b& the second, merely an evenly progressive ossifying considered seriatim. process in an Moreover-and this incomplete stage. Characters. was my main object-mistakes can seldom arise Physical in palpating these bones. The normal parietal at The atrophy occurs as depressions found on the the period in question is rigid, and the only spot inner aspect of the bone. The atrophic areas show where localised yielding due to immaturity is liable both lacunar and diffuse formations, both being to occur is a small area about the parietal in the same bone. The lacunar symmetrical " frequently present foramina. These foramina, or the " sagittal foramen areas occur as membranous spots isolated in the bone, replacing them, lie about 1 to 1¼ inches from the or it may be abutting on its margins here and there. posterior fontanelle. The sense of weakness at this Their edges show a thinning down of the bone to point is due to irregular spacing of the spiculæ near the membranous or semi-membranous centre, which the margin. Except for this, which is easily excluded, centre varies in my specimens from about 0’5 to the parietal at about term presents no feature due 2-5 cm. in greatest width. The diffused areas may be to absolute immaturity which could simulate cranio- membranous in part or wholly, or merely so far tabes. Yielding of large portions of the periphery atrophied as to yield with ease. Where the bone is like that normal at the seventh month, and due to reduced to a thin shell, but not entirely lost, and is relative immaturity, is rare enough to be a curiosity, palpated in situ through its integuments, it is apt and in any case could not well be mistaken for any- to feel " leathery," though still resilient; areas " thing else. In examining many of these bones, a of total atrophy feel flaccid or parchmenty," degree of weakness sufficient to cause doubt is according to their state of tension. Any part of the occasionally met with along the anterior half of the parietal may be involved, but in all cases I have inner margin. This I at first thought to mean recorded the site of election has been the inner half, immaturity also, but the X ray reveals an early and especially its anterior two-thirds. In 76 instances stage of diffuse atrophy. Such cases, in fact, occupy (66 in vivo) the parietal was affected in all, the right an intermediate position towards clinically obvious alone in 27, the left alone in 13, both bones in 36. craniotabes, but need not be taken stock of in com- In 2 the upper portion of the frontal was also involved. piling morbid series. The squamo-temporal and squamo-occipital were not There is thus no practical source of fallacy in found implicated in any. diagnosing craniotabes in the newborn by clinical Palpation is sufficient to settle the fact of atrophy, means. and to determine its main features ; but in detail Craniotabes in the Fœtus. it is inaccurate, and this must apply also to palpation I shall throughout use the term craniotabes of infantile craniotabes. Parts bridged by bone are to denote a craniatrophy which has reached a apt to yield like one, and adjacent bone, especially clinically recognisable degree, and which is dis- on the peripheral side, through loss of its normal FIG. 3. FIG. 1.

Fm. 2.

Repair proceeding in a large circular aica Parietal bone of subject at term with cranio- at birth. tabes, Note predominance of atrophy in anterior two-thirds of internal segment. A normal parietal at term (vertex presentation). covered of the by gentle palpation bone in situ. i sometimes seems to to the The term " infantile craniotabes " will be used support, belong atrophied to ’ area. For this reason my previous illustrations, denote a craniotabes which first at appears some based on results of time after birth. palpation, represent very imper- fectly the true state of things. The radiograph now The prevailing opinion, as reflected in text-books, shown is sufficiently illustrative, though the definition &c., is that craniotabes is a condition developing in might perhaps be improved. (The low density of and it is so described. Some have remarked infancy, these bones entails the use of a very " soft tube.) on the occurrence of defects at and bony birth, For comparison, a normal at term is included, ascribed them to The existence parietal bone-immaturity. and one showing infantile craniotabes taken as figured also of a condition at birth deemed to be craniotabes from Carpenter’s book on syphilis in children, and has been recognised by some authors, but, so far as given by the author to illustrate that form. I am as a found this aware, rarity. Having latter Details. condition congenitally with some frequency, and I Macroscopic excluded immaturity, my wish was to ascertain In parietals at birth showing normal ossification whether its analogy with the infantile form was the vascularity of the bone may appear uniformly anything more than a superficial resemblance. distributed, or show a degree of irregularity in this Evidence was then obtained which collec- In those gradually i respect. showing craniotabes, however, tinely afforcls a sufficient proof of the identity of the there is sometimes, not always, definite hyperæmia DR. E. HUGHES: CRANIOTABES OF THE FŒTUS AND INFANT. 1047

with an irregular distribution. This is best seen in occurring in the newborn do not mean craniotabes more advanced examples, and after hardening, when because they occupy a different part of the bone. their dark colour is in sharp contrast with the appear- This latter is also an error of fact, as they may be ance of normal specimens. The hyperæmia is seen found in the same part, but the observed differences to be more pronounced in a broad zone round the of position at the two periods is exactly what would atrophied parts. The pericranium is not noticeably be expected if the two conditions were identical. At thickened. This structure is often ill-developed at both periods they occupy the most dependent regions birth, and may not strip very easily off a normal bone. of the skull, the regions of maximum strain. Again, It usually strips off an atrophied site, though the it is a mark of a true cause (in action) that when presence of old blood may cause partial adhesion removed its effect (if impermanent) always begins and pigmentation. The same description applies to cease from that time forward. Events were to the dura, which, moreover, is thinned over mem- followed in some fifty or more of my cases, and in all branous sites. One naturally thinks of intra-partum progressive repair was observed to take place where is the the fcetal area was situated FiG. 4. (as usually case) outside the new regions of pressure after birth. The physical characters tell the same tale. In the normal majority of skulls at term, the indentations accommodating the cortex are as yet ill-marked and scanty. Craniotabes (in general) implies a morbid exaggeration of these in dependent parts. For the foetus, and in head positions, one must infer a double force of compression-tension for both inner and outer strata. The design of the parietal bone bears out this inference, at any rate for the outer stratum. There is, of course, no diploëic space at this age. The inner layer is thin and compact ; the outer layer, in contact with the inner, and about two to three times its thickness, I find to show partial interlacement of the radiate fibres, together with a general tendency to slant from the inner towards the outer surface from centre towards periphery. This latter arrange- ment, so far as it exists, would tend to equalise strains from external pressure, and to transfer them towards the stronger interior bone. Owing to the Part of parietal showing infantile craniotabes. (From Carpenter.) general structure, external compression strain would tend to be transferred to the apex of a wedge of strain in these but in confinement series damage cases, my whose base is on or faces the margin, and this, so one stillbirth from unrelated only occurred, probably far as there is need to assume it, would help to explain the others seemed none the then or causes ; worse, the frequent occurrence of atrophic holes in the afterwards. Though numbers have been re-observed interior. Internal compression by the semi-diffluent at later ages, no evidence of cortical injury has been brain-mass of the foetus should be moderately uniform, met with. The the intra- following shows, however, but with a gravitational stress concentrated on the partum possibilities in a rather extreme case-a still- inner segment. The greater tendency to diffused and born female infant in series :- my laboratory other atrophy in this segment is, no doubt, thus There was much inner of both segment atrophy accounted for. One can only the main diffuse and The left showed postulate parietals, chiefly partial. features of so irregular a mechanical system as this, a fracture 1 inches in length, parallel with the sagittal whose complexity is increased by the various foetal - edge and involving the thinned bone near its junction movements, and by such developmental variations with normal bone. The here was torn pericranium as may occur in the bones themselves. There is through, and a layer of recent blood extended beneath further to be included the inconstant lie of the head it as far as the eminence. The underlying dura, in relation with the uterine wall, the obliquity of otherwise uninjured, was separated from the bone the uterine axis, &c. The greater implication of by blood and serum (commencing internal cephal- the is of interest in connexion with Further both dura and right parietal hasmatoma). forward, peri- the lower lie of that bone so far as gravitation is cranium were partially adherent to the atrophic concerned, in first positions; while the general bone up to the fontanelle, the adhesion being due to anterior position of these atrophies together with a thin deposit of old (ante-partum) blood. The other points should help in determining the normal cortex was subjacent apparently undamaged. stresses on the foetal head prior to labour. I have One would expect sub-pericranial haematoma after found craniotabes in births the vertex. Its the birth of tabetic where only by severely skulls, especially occurrence in other than head presentations would the margins were diffusely atrophied. Of 11 examined indicate that the foetus had recently changed its post mortem, three showed atrophies of this type, position. and in all three there was haematoma. commencing Clinical Course. Till recently, the significance of this point had unfortunately escaped me, so that the absence of Rigidity of the foetal area removed from stress is record of it among those that survived may mean generally accomplished, clinically speaking, by the a fact or an omission. As this accident, however, end of five weeks, but repair may be much more probably occurs in under 1 per cent. of all births, gradual and prolonged to three months. The finding it is unlikely to. complicate these cases with any of areas far forward during infancy, if this is not frequency, at any rate to a clinically obvious degree. far advanced, would mean their origin in the foetus. But when present, especially on both bones, the During the first four months of infancy fresh areas possibility of underlying craniotabes may be borne in the posterior segment are very liable to develop, m mind. The histology of these bones will be given and the case then becomes one of infantile cranio- in a later note. tabes, which subsequently runs its usual course. Mechanical, Catisatioit. This sequence occurred in 33 out of the 38 which I This is the only certain element in the causal was able to follow up. Of 117 born without recog- nexus of craniotabes in general. Yet that it has nisable craniotabes, and followed to some part of the sometimes been disregarded is shown in the statement fourth month, 10 afterwards showed it. Allowing of Carpenter2 that craniotabes (infantile) cannot be for modification by larger figures, the discrepancy a sign of rickets because it is getting better while found (about 86 as against 8 per cent.) is still great rickets is developing ; and by an argument quoted enough to justify my inference that the bulk of :from Wieland that the imperfectly ossified areas infantile cases are recruited from those showing 1048 DR. E. HUGHES: CRANIOTABES OF THE FŒTUS AND INFANT.

recognisable craniatrophies at birth. This is well decalcification must, be promoted bv some morbid explained for many by supposing the skull at birth agency. Here I shall deal with syphilis and rickets already prepared for further craniotabes by a degree (or rather, the as yet unknown causes of rickets) t as of atrophy in the posterior segment as yet unrecog- possible morbid agencies, in the light of such data as nisable to palpation, and not to be detected by any the present inquiry can contribute. I find it possible but radiographic means. It is, moreover, in this for a child to have foetal followed by infantile cranio- quadrant, part of the segment most prone to atrophy tabes, and to pass through infancy and earlier child- in foetal life, that I find infantile craniotabes to more hood without showing any sign of either disease; commonly begin. It may also be observed to start but this observation has little real weight. ’Rickets from the thinned margins of small atrophic areas may be arrested before it is clinically demonstrable, found in the posterior segment at birth. Such con- and syphilis may remain clinically latent. Most siderations may explain why most infants escape craniotabetics show either one or both; and by post-natal craniotabes, though subject to like con- different schools of opinion the causality of both, ditions. But it may be also plausibly argued that separately or combined, has been asserted, though the organic causes’ of decalcification present in the as a rule with little serious attempt at proof. The foetal state are carried on into infancy. problem is by no means an academic one, seeing the Enough has now been said to indicate that the therapeutic needs of child and mother on either inception of craniotabes as a pathological event must assumption, and the importance to the theory of be relegated to foetal life, if not always, then very rickets of a decision on the matter. often. In connexion with the whole argument the Regarding syphilis first, its relation is beyond absolute frequency of pre- and post-natal forms needs dispute, for it is consistently present in series, includ- to be worked out. My own figures (industrial popu- ing my own, to as much as 50 per cent. or more. lation of Liverpool) give so far for all grades of the These findings, moreover, are based on clinical foetal form 21-6 per cent. (60 out of 277 unselected evidence, and a positive residuum over and above vertex births). A series of still-births furnished ten this must be allowed. From historical analogies, examples in about 63 (in a few of these the presenta- the argument, therefore, seems a fairly strong one tion was uncertain). For the infantile form a recent for the necessary antecedence of syphilis ; but the probable estimate by Wieland4 gives about 20 per connexion needs examining further. Carpenter, who cent. of all infants, presumably studied in a city devoted long attention to this subject, estimated that district. These figures, so far as they go, tend rather about 50 per cent. of congenital syphilitics show to support the thesis just advanced. craniotabes. If the above estimate of about 20 per Infantile Craniotabes. cent,. of all infants is also near the mark, we should then be required to assume that some 40 per cent. of material here is 109 cases, but any My deficiency infants, in our city populations, are born with syphilis in of numbers has been, as I venture to think, point -an estimate very in excess of any yet made more than for the method of con- widely compensated by on other clinical or tinuous and intensive to individuals. grounds, pathological. study given The same observer prepared charts showing the Results as to localisation agree closely with those of coincidence of craniotabes with the manifest who found the seldom affected syphilis Carpenter, occipital of the earlier months.7 Granting the coincidence en in with the In all my cases comparison parietal. masse, we have yet a very good mechanical reason where the was affected, there was at some occipital for the of craniotabes at these ages, time more or extensive in the predominance pronounced atrophy from the of an and there was evidence or that the quite apart activity accompanying parietal, proof moreover, the coincidence disap- former was involved in of time. syphilis ; largely secondarily point pears on going into detail. The maximum of each The occipital, however, may be the last to heal. is reached at different and if indivi- The statement of Stoeltzner5 that craniotabes is generally times, only duals are studied in their craniotabes is found after the first three months is contradicted I continuity, by found to have an determined the independent career, by my results, numbers developing during second the conditions. craniotabes shows month. The earliest in the fourth the pressure Moreover, began week, indifference to an otherwise successful course of latest at the end of the fourth month. Most, however, mercury. This rule has been uniform in my experi- reach a maximum this latter age, and thereafter by ence when cases are chosen at the right time, say begin to regenerate. The mechanical conditions those in the second which furnish the to the of incidence. Relief of starting month, nearly key period will in natural course. It is useless is about earlier in some than always spread pressure brought others, to select cases at the of natural since but in most is or before period healing, sufficiently accomplished by this on at rates. - It is also noteworthy the end of the fifth month. we find goes differing Accordingly that extensive cases sometimes run their whole craniotabes after this relief disappearing time, given course without of In 10 still- of whatever the child’s state of health any sign syphilis. pressure, may born instances S. was not found in be. has been felt some 6 in examined, pallida Difficulty by assigning liver, and and the Wassermann reaction, the same to diffused and lacunar forma- spleen, lung, pathology taken in was tions. This I do not since the same case 9, negative.t share, may While such with other the lacunar form when it the diffuse considerations, together represent begins, not now all to discredit the form at its full and the lacunar form points enumerated, go development, causal of its more remote as it heals. In areas remnants agency syphilis, causality again widely atrophied, could not well be excluded so as we are of calcified tissue are often and long largely partially left, regenera- of its of the foeto-infantile tion occurs from these as well as invasions ignorant power injuring by irregular mechanism of and while it seems of bone from the centre of ossification. The result calcification, that some cases of low virulence and is that a trabecular of new possible latency broadening arrangement our methods. I find bone is to be formed, escape present it, however, apt enclosing ever-dwindling more rational to its action in that kind as If the case is first seen in this last regard atrophied spaces. and its association with as it sui since nonspecific, craniotabes phase, may appear generis, especially the same as its manifest rickets be at these The having meaning association with may present ages. which in the human is variations in contour of the back of the skull rickets, subject deceptively may the action in both conditions to be held for some of the varieties in form close, being promote responsible of bone. In other were it not for and position met with. resorption words, the presence of syphilis, many of these craniatrophies Organic Causation. would not have time to reach a degree where they The mechanical causation of this curious condition can be clinically recognised. is a of a causal nexus. the clearly only part Though t All that is up to now determined is the agent, or one of the great majority of individuals are subject to closely agents, preventing rickets. The causes producing it come into similar mechanical conditions, only a minority-say play after the preventing agents are removed. These causes to the arc unknown. one-fifth-develops craniatrophy clinically t have Prof. Beattie’s permission to mention these results, recognisable degree. In this minority, therefore,, which were obtained in his laboratory. DR. F. G. CANVSTON: ANTIMONY & EMETINE IN BILHARZIA DISEASE. 1049

Regarding rickets, my observations suggest that some 16 hours out of each 24, the total stress being it is clinically associated with much the same probably greater then than after birth. Add to frequency as syphilis. Though the severity of cranio- these considerations the partial immunity of the tabes and a subsequent rickets often varies directly, foetus against adverse maternal influences, and the this ratio is quite inconstant. The feeding in 105 possibility, by analogy, that any such effects might cases when first found with infantile craniotabes be shown in a modified form at these early periods, (extreme ages 1 and 9 months) was: exclusive and the difficulty becomes, perhaps, less formidable. With this particular problem, however, observa- tion can do little, and one awaits the results of the experimentalist, especially on such subjects as the effects on the foetus of ill-balanced maternal diets involving deprivation of vitamin A, and the causes of osteomalacia. References.-1. THE LANCET, June 13th, 1918. 2. Brit..Tour. Child. Dis., February, 1908. 3. Findlay, L., Med. Research Com., Special Report, No. 20, 19. 4. Ibid. 5. Pfaundler, M., and Schlossmann, A., Dis. of Ch., 1912, vol. ii., art. Rachitis. 6. Still, G. F., Disorders of Childh., second edition, 73-4 ; Cautley, E., Dis. of Ch., Garrod, Batten, and Thursfield, 1913, 112. 7. Reports Soc. Study of Dis. in Child., vol. iii., 215, 299, &c. ______

ANTIMONY AND EMETINE IN BILHARZIA DISEASE. BY F. G. CAWSTON, M.D. CAMB. IN 1917 Dr. J. B. Christopherson established tartar emetic as the routine treatment for bilharzia disease in Egypt, and no equally effective but less toxic preparation of antimony is at present available. Undesirable results of unskilful administration of the drug are still being experienced in various parts of South Africa, the solution causing necrosis through being injected under the skin instead of into the blood stream. Sometimes large doses are given before the 28 16 21 24 25 20 18 23 22 19 26 27 usual tolerance for the drug has been acquired, and FIG. 5.-Chart showing the months of birth of 123 craniotabetics. occasionally the doses given are too small to produce breast-feeding, 62 ; mixed feeding, 14 ; exclusive any appreciable effect on the parasites. hand-feeding, 29. In the breast-fed the atrophies During 1920 I recorded my results obtained by a number of cases of bilharzia disease were not less extensive, but usually partial in degree. treating by intravenous of a solution of That so many were breast-fed is against expectation, injections freshly prepared tartar the on alternate but it may be argued that, ceteris paribus, if the emetic, injections being given maternal blood cannot prevent craniotabes the days shortly after a light breakfast, the dose varying maternal milk will not be able to prevent it afterwards. from gr. to 1½ gr. The doses were gradually increased until the dose that the could comfort- The point on which observation can best help largest patient was reached. theory appears to me that of seasonal incidence. ably tolerate The subsequent history of these and other cases show where the This is now being worked out. The results so far are that, are over a of 28 shown herewith, though their inadequacy as yet is injections given regularly period days, patent. The month of birth is stated for 123 in there is little possibility of a return of the symptoms. which it is known. The infantile series includes A dose of more than two grains is unnecessary ; doses do not to effect a cure more cases only observed with that form. In the foetal larger appear any It is to discontinue treatment cases (58) an error involved in such estimates can be rapidly. always risky before the or checked by knowing the number of births per month 28th day to give the injections less than three times a week. I have seen among which they occurred (see foot of chart). frequently recurrences 15 have been over It seems, therefore, that a seasonal curve may when gr. administered a of 24 and others where four have exist. Thus 51 per cent. of the foetal series, and 60 per period days days been missed in middle of none cent. of the infantile, were born in the last four the treatment, but where treatment has been continued without inter- months of the year. Supposing the bulk of foetal for 28 even no total dose cases to show infantile recurrence, it would follow ruption days, though greater that infantile craniotabes will be chiefly met with, has been given. The was dissolved in from 4 to 12 c.cm. of at any rate in its worst degrees, in the first few powder distilled water before drawn out months of each year. boiling just being up of a wide-mouthed test-tube into an serum If a marked winter aggravation is confirmed by all-glass which had been sterilised and had a larger figures, it will serve to that extent to ally syringe already craniotabes with rachitic phenomena in general. suitable needle attached. It has always been my But the chief remains. We have seen that practice to boil both needle and syringe before use, difficulty and to the skin with rectified before the early disappearance of craniotabes is no obstacle paint spirit the and I see no reason to alter this to its acceptance as a true of rickets ; but its injecting needle, sign Without the early appearance constitutes a difficulty which has procedure. discolouring skin, spirit already existed for the earlier infantile examples, rapidly produces a clot which helps to arrest bleeding and is only somewhat increased by bringing in the and assists in rendering the seat of injection both last few weeks of pre-natal life. A partial solution aseptic and anaesthetic. Incompletely cured cases of may be attempted, however, by recognising the bilharzia disease are especially liable to attacks of mfiuence of stress on the individual bones in deter- renal colic, and when the general health does not mining the order of rachitic bone changes in rapidly improve after treatment it is generally because general. all the have not been These Such knowledge as we have indicates that the stresses parasites destroyed. attacks of colic which sometimes occur the on the fcetal long bones are generally less intense during than those obtaining in the outer world. But the course of treatment are probably due to an accumula- stress on the dependent cranium must be consider- tion of incompletely destroyed ova in the kidney able, both by its position in the relatively rigid lower substance, which, under ordinary circumstances, uterine segment, and by the interior brain-mass for 1 THE LANCET 1920, ii., 392.