W.Colin Mackenzie
1916 The Lancet  
183 eight cases in which the serum was tested at various intervals of from ton minutes to three hours after the administration of the drug four were found to have developed no recognisable increase of bactericidal power. Three of these were tested against cultures of staphylococcus, the other against the pneumococcus ; one of those tested against the staphylococcus was also tested against the pneumococcus with a similar result. Of the other cases three showed a slightly increased bactericidal
more » ... ased bactericidal power, in one case against the staphylococcus, in another against the pneumococcus, and in the third against staphylococcus and streptococcus. The remaining case showed a similar slight increase of bactericidal power against a culture of streptococcus, but none at all against either staphylococcus or pneumococcus. It was noticed, however, in all these experiments, and especially in those in which staphylococcus cultures were used, that the samples of serum obtained after the injection of the salvarsan showed a marked power of inhibiting the growth of the organisms. This was evidenced by the slowness of growth-two or even three days elapsing before it could be definitely ascertained if growth was present or absent; and also in those tubes where growth occurred the organisms were agglutinated into masses, so that instead of an even turbidity of the broth a small mass of organisms occurred in the bottom part of the reservoir. In view of the fact that the patients' serum in our experiments always showed a higher bactericidal power after the injection of neosalvarsan than of salvarsan, it is of interest to note that Swift and Ellis,3 working with Spirochaeta duttoni, were able to show a similar difference in respect of spiro-chæticidal power. Further, they showed that patients' serum, after administration of these drugs, acquired a spirochæticidal power for only a few hours, reaching its maximum within the first hour after the injection; and that this spirochaeticidal power was somewhat increased, rather than diminished, by heating the serum to 60' C. (cf. Table V. above). Szcrjamary and Conclusions. 1. Neosalvarsan and salvarsan in watery solutions possess a very distinct bactericidal power against staphylococcus when the strength of the solution is 1 in 6000. When the solvent largely consists of blood or serum this power is slightly diminished. The bactericidal power of solutions of both these preparations appears to be practically the same. 2. The administration of neosalvarsan in ordinary doses renders the blood fluids markedly bactericidal This power lasts but a short time, and seems to reach its maximum about one hour after the administration of the drug, diminishing rapidly in the third and fourth hours. 3. Heating the serum to 60° C. for from 10 to 20 minutes has no deleterious effect on this bactericidal power, showing that it is not in any way due to the development of immune bodies in the serum, and this fact, together with the short period in which the serum is found to be bactericidal, strongly suggests that the bactericidal power is due to some arsenic compound in solution in the blood serum. 4. Salvarsan which, as mentioned above, has almost identically the same bactericidal power as neosalvarsan in in vitro experiments, gave practically no demonstrable bactericidal power to the 3 Journal of Experimental Medicine, Oct. 1st, 1913. patient's serum when ordinary therapeutic doses were administered, but it was constantly noticed that organisms which had been treated with serum obtained within three hours of the administration of the drug grew very much more slowly than normally and were agglutinated into masses. 5. In view of the very distinct bactericidal power which the serum acquires after the administration of neosalvarsan, it is reasonable to hope that the administration of this drug, or some similar preparation such as neokharsivan, would have a beneficial effect on wound or other similar septicaemias, and might even strikingly assist in the sterilisation of deep and irregular suppurating wounds. A STUDY of the fauna of Australia offers a unique opportunity in aiding the solution of many important biological questions, and especially those pertaining to the gastro-intestine. The two monotremes and the various marsupials represent the selected results of a struggle with forces that have been operating through many ages. As the survival results among the marsupials are in many ways so diverse we have a distinct advantage in being able to institute comparisons among animals limited to the same order. Furthermore, during the last century these animals-lowest on the mammalian scale-were suddenly brought into contact with modern man. We are unfortunately now witnessing final phases in the struggle and their biological significances. Amongst the marsupials we have on one side the koala, a purely eucalyptus-leaf feeder with a csecum which may reach the great length of 244 cm., and on the other the Tasmanian devil (Dasyurus ursinus), purely carnivorus, which has evolved a simple intestinal tube swung on a single mesentery, with no differentiation except microscopically between the large and small gut. Both these are rapidly becoming extinct-the former in spite of a rigid protection. Between these varieties we have the opossum (Trichosurus), more adaptable as regards diet than the koala, and hence still numerous in different parts of the continent, and the allied varieties of the Macropodidæ-viz., wallaby, the selected and more adaptable variety whose caecum may resemble that of the human foetus and be only 5 cm. long, and the kangaroo whose caecum-much more capacious-varies from 30 to 40 cm. In addition we have Phascolomys (wombat), the selected marsupial, living on a nutritious diet of vegetable matter, whose abdominal contents resemble those of man and who shares with him and the higher anthropoids the possession of a true vermiform appendix. To those I propose to add the Echidna. What is meant by Vermiform Appendix. The appendices of these four types apart from size are difficult to differentiate, and subscribe to what Charles Bell and Owen refer to in the definition of the vermiform appendix as a small gutappended to the caecum and differentiated externally by a marked commencement and internally by a valvular structure-but bearing no relation in size or figure to any part of the intestinal canal, which, from its smallness and twisted appearance like the writhing of an earthworm, has received the name of 184 " vermiform." As Stapley and Lewis in their important paper write: "It did not occur to Owen on account of the presence of this massed lymphoid tissue to name the end of the rabbit's caecum 'vermiform.' He did not regard the rabbit as showing that rare form which he thought of under the name 'vermiform appendix."' The rabbit has a highly specialised intestine, since apart from the sacculus rotundus there are no less than six distinct areas in the great intestine, making it unfit for comparison. Nor did Owen include Lemuroidea, as in his description of the aye-aye he is careful to point out; nor did he refer to the appendicular ends of cæca such as one often sees in the phyllophagous koala and opossum, where I have never yet found a single lymphoid follicle. The Validity of Einar Lönnberg's View. In 1902 Dr. Lonnberg advanced the opinion that if the wombat's appendix were a true vermiform appendage-i.e., the reduced blind end of a cæcumit ought to have opened into the caecum of which it was a part; as it does not, but opens with a quite independent opening of its own near that of the ileum, he judges that the so-called processus vermiformis of the wombat represents a rudiment of the whole caecum; since it acquires a similar situation, opening into the colon in relation with the ileo-cæcal valve. A new caecum becomes formed behind FiG. 1. Ileo-caecal region, Phascolomys mitchelli. (All the figures are half natural size.) the caecum, the result of a bulge of the colon owing to food alterations-viz., reversion to a more bulky diet. Apparently Lonnberg's material was limited, as he tells us when discussing the colic sacculi he had worked on two animals, and further, his description might equally apply to the fourth variety of the human caecum in which, according to Deaver, the internal sacculus has disappeared entirely and the base of the appendix is attached to the caecum posterior to the receding angle between the ileum and the caecum, the opening being sometimes in relation with the ileo-cæcal valve. Furthermore, we have no evidence that food alterations presumably recent have occurred. A reference to Figs. 1 and 2, in which the lumen of the appendix is patent, indicates the rotation taking place, and shows the base of the appendix corresponding to the true apex of the caecum. In Fig. 3 , where the internal opening which was not within the lips of the ileo-caecal valve has closed and 1 the appendix is adherent to the ileum, not only has the left sacculus disappeared, but the right has atrophied almost up to the level of the ileum. The average human csecum, i.e., one approaching the fourth type, has a depth of about 6 cm., and in the case of a young orang-utang in the Hunterian Museum the depth of the caecum is 2'5 em. and the width 4'5 em. It approaches the fourth type-the termination of the ileum running obliquely through the intestinal wall being in FIG. 2. Ileo-caecal region, Phaseolomys mitchelli. juxtaposition to the appendicular orifice. An examination of a series of 12 Victorian wombats showed that the csecal depth varied from 1 to 1'5 cm. In two cases it was only 0'5 cm. and in one case was actually on the ileal level. In a latifrons with a well-defined lumen, mesentery, and appendix the pouch was 3 cm. deep, and in another (mitchelli) with the appendix obviously the apex of the caecum the depth equalled 4 em. and the width 5 cm. The lumen of the appendicular canal was incomplete in 64 per cent. of specimens. After the twentieth year 32 per cent. of human appendices are obliterated. The approximation of the base of the appendix towards the ileo-caecal valve is quite in accordance with the evolutionary trend of that organ. Lonnberg believes such a movement took place. Yet he would not admit of the classification of the wombat with man and the ape, because FIG. 3. Ileo-cæcal region, Phascolomys mitchelli. he believes a new caecum has been formed, the result of supposed diet alteration. To favour that view from the examination of a large number of specimens I have failed to find evidence that, apart from the formation of a new caecum, even the right external sacculus has enlarged. On the contrary, there is abundant evidence of atrophy. (Figs. 3 and 4.) Owen's generalisation,3 that "the caecum in the wombat is extremely short but wide; it is 3 Comparative Anatomy of the Vertebrates, vol. iii. 185 remarkable for being provided with a vermiform B appendage," must still be accepted. Types of Fluman Ccecuma. The classical description of Sir Frederick Treves4 still forms the basis of our comparison. He recog-r nised four types: (a) Infantile, with muscle bands equi-distant ; (b) caecum more quadrilateral, t appendix appearing between two bulging sacculi ; i (c) apex turned to the left and posterior-the base of the appendix is brought nearer the ileo-coecal ] valve, a false apex formed by the highly developed part to the right; (d) sacculus to the right relatively large, while that to the left has disappeared -the root of the appendix appears to spring almost from the ileo-emeal junction. No anatomist has ever suggested that the relatively large size of the right sacculus was the result of some reversion to a more bulky diet. These four variations become intelligible-not mere statements of facts-if we recognise that each represents a coordinated sequence of the other; each is part of a coordinate scheme in the evolution of the appendix, and no one variation can be regarded as the type. Mode of Disappearance of Structures. It is interesting to note that the oldest known wombat's appendix, once the property of Sir Everard Home, is in the Hunterian Museum, and that John Hunter was known to be engaged on the marsupials just before his death. His work on absorbents shows that the question of disappearance of organs interested him. " It may be difficult at first," he writes, "to conceive how a part of the body can be removed by itself, but it is just as difficult to conceive how a part can grow or add to itself, which we see daily taking place. These are both certain facts. A part which was necessary in one stage of life, but which becomes entirely useless in another, is removed. It is evident in many animals the thymus gland is removed." It is clear that a knowledge of the mode of disappearance of normal structure should help us in the investigation of the abnormal. Amongst the marsupials we notice the disappearance of the thoracic thymus in the wombat, but its good development in the Dasyurus ursinus ; the closure of the inguinal canal in the male sex of the latter though open in that of the former as well as in koala and the kangaroo ; the incorporation of the fibula into the tibia as seen in the Macropodidæ ; the small relative size of the adrenals in the phyllophagous koala and Trichosurus and the approach of the right along the vena cava to the liver. In the case of the opossum (Trichosurus) it may be found approximate to the liver under the capsule or be completely absent. In the female the Miillerian ducts, though differentiated into duct, uterus, and vagina, nevertheless open separately into the urino-genital sinus. Yet from the upper part of the vagina on each side we have given off-beginning as a bend-the median vaginal caecum which approximates so closely to that of the opposite side that fusion takes place-the two walls forming only an intermediate septum. This breaks down so that one central vaginal caecum or median vagina is formed, which, increasing in size, reaches the urino-genital sinus to serve for the transmission of the foetus and remains the vagina of higher types.5 Thus we see formation and atrophy going on in the one order and the triple vagina of the marsupial becomes intelligible when 4 Hunterian Lectures, 1883. 5 Proc. Linnean Soc. N.S.W., 1899 and 1900, Professor J. P. Hill. we roalise that the design is unification-the lateral vaginæ finally disappearing. Similarly by a study of the vermiform appendix in the wombat nature offers us the clue to the mode of disappearance of that structure in man since we can trace it from the fourth human type to complete disappearance (Fig. 4) . It may be found as in Phascolomys latifrons quite independent of the ileum with a well-defined mesentery, or the mesentery may be only partial and the base be in relation with the termination of the ileum or the mesentery be altogether absent. As shown in Fig. 3 , the appendix finally becomes incorporated into the wall of the ileum and the various grades are seen till in one specimen no appendix is present -the only structure being a firm knob on a shred of mesentery. In none of these specimens was there evidence of any inflammation. Thus a complete coordinated sequence from the foetal or FIG. 4. Ileo-cæcal region, Phascolomys mitchelli. infantile type of caecum to one showing complete disappearance of the appendix is clearly demonstrated. In the wombat about the ileo-cæcal region a puckering is noted, producing sacculi and depression. This is of interest when we consider that close together about the root of the mesentery we have duodenum, duodeno-jejunal flexure, transverse colon, and with an interval of only 2'5 cm. the ileo.cæcal junction. This association I regard as being dominated by the right vagus nerve. Ccecal Region in the Monotremes. When we consider the aeons that have passed since the monotremes first evolved we have reason to congratulate ourselves that two, presenting such diversities, have remained-one the Platypus, content to remain in the mountain streams, and the other the Echidna, evolving on land, where the struggle for existence was more intense-thus no doubt accounting for the greater size of its brain and the development of convolutions and sulci. The intestinal tract in Ornithorhynchus might be described as a simple canal 5-6 feet in length
doi:10.1016/s0140-6736(00)53014-1 fatcat:uj3w2xhm6bgv3l2ahukl6mhode