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2. On an Aerotonometer and a Gas-burette.1

By Professor LÉON FREDERICQ, Liège.

The air which enters the lung is rich in oxygen (20.9 per cent.) and poor in carbonic acid (0-03 per cent.). On leaving the lung it is relatively poor in oxygen (18 per cent. in dogs) and rich in carbonic acid (2 to 3 per cent. in dogs). It has given up oxygen to the blood and received from it carbonic acid.

What is the cause of this gaseous exchange between the blood and the air of the pulmonary alveoli? Pflüger believed that he had succeeded in explaining this exchange by the simple laws of gaseous diffusion-laws in virtue of which each gas passes from a medium in which its tension is high towards a medium in which its tension is low. The determinations of carbonic acid tension made by Pflüger's pupils simultaneously in the blood by means of the aerotonometer and in the air of the pulmonary alveoli were in complete harmony with this explanation.

Christian Bohr has come to a different conclusion on this subject. According to him, gaseous diffusion alone does not explain the exchange of gases between the blood and the air of the lung. Bohr has found in several of his experiments the air of the alveoli richer in oxygen and poorer in carbonic acid than in the arterial blood leaving the lung. According to Bohr, the tissue of the lung plays an active part in respiration: the pulmonary epithelium excretes carbonic acid by a true secretion process, and passes oxygen into the blood, not in accordance with the laws of diffusion, but against these laws.

I have recently taken up this subject again, and in doing so have made use of the aerotonometer exhibited to the Section, which is a modification of the instrument of Pflüger. The apparatus consists essentially of a sufficiently long vertical tube, connected above with the carotid of a living animal (an anesthetised dog), and below with a vein. The arterial blood (which has previously been rendered incoagulable by the injection of propeptone) flows continuously over the inner surface of the tube of the aerotonometer, which is kept at a temperature of 38° C. If the experiment lasts sufficient time for the attainment of equality of tension of the gases of the blood and those enclosed in the aerotonometer, an analysis of the latter gases will indicate the tension of the gases of the blood. Bohr believed that equality of tension could be reached in a few minutes, and thus obtained erroneous results. I have found that nearly two hours are necessary before equality of tension is reached. One finds then that the air of the aerotonometer contains 2 to 3 per cent. of carbonic acid and 12 to 14 per cent. of oxygen, representing the tension of these gases in the blood in accordance with the diffusion theory. I have also found that if one lets the animal breathe pure or nearly pure oxygen, the tension of this gas in the arterial blood may exceed 60 per cent. of an atmosphere. The animal, nevertheless, shows only a slight tendency to apnoea; it continues to breathe. Apnoea is thus not a necessary result of a very high oxygen tension in arterial blood. This is a fact which seems to me very important in connection with the theory of apnoea.

The gas analyses were made with a gas-burette, shown to the Section, which is simply a modification of that of Hempel. The burette is drawn out at the level where the readings are made, so as to permit of reading easily to 02 or '01 c.c. The confining liquid is water (and not mercury), which gives rise to scarcely any error, diffusion of gases into liquids being so slow. The carbonic acid is absorbed by potash solution, the oxygen by phosphorus.

3. On Local Immunity. (A Preliminary Communication.)2 By LOUIS COBBETT, M.A., M.B., F.R.C.S., and W. S. MELSOME, M.A., M.D, If it be true, as there seems reason to believe, that recovery from an infectious disease is due to certain changes in the body, which make it more resistant to the micro-organisms which cause that disease, and that the same changes are also the

For further details see Centralblatt für Physiologie, 1893, vii. p. 26; 1894, viii. p. 34. ? A full report is published in the Journal of Pathology, 1894.

cause of subsequent immunity, the well-known fact that in erysipelas the parts first attacked may be recovering while the disease is spreading elsewhere would lead us to suspect that these parts have learnt to resist the streptococcus while the rest of the body is still susceptible.

To inquire whether erysipelas confers any such local immunity was the object of the following experiments:

Fourteen rabbits which had recently suffered from erysipelas in the right ears were again inoculated with the streptococcus, this time in both ears. In each case a control animal, inoculated at the same time, suffered from typical erysipelas. The results were as follows: Left ears.—In four, only a little redness about the seat of inoculation. In four, erysipelas commenced, but aborted on the third or fourth day. In six, typical erysipelas. Right ears.-Inflammation rapidly appeared, affected the whole part, and subsided in twenty-four to forty-eight hours. Culture experiments, which invariably revealed the presence of streptococci in the early stages of true erysipelas, showed that micro-organisms were absent from the inflamed right ears. Thus all the right ears showed themselves to be immune, while nearly one half the left ears proved as susceptible as those of the control animals. Hence we conclude that the first attack of erysipelas had conferred a very complete local immunity. That erysipelas confers some degree of general immunity is already well known from the work of Fehleisen, Roger, and others.

Further experiments showed that this local immunity lasted only so long as any thickening remained in the ears after erysipelas. Its duration depended, therefore, on the severity of the first attack.

The inflammation which resulted from inoculations of ears previously affected we thought to be a reaction against the poisons actually introduced, and not due to the vital activity of the cocci, because we could obtain no evidence that these had multiplied and invaded the ear. This opinion was put to the test by injecting into both ears of animals, which had recently suffered from erysipelas in one ear, sinall quantities of concentrated filtered cultures, and in one case the streptococci themselves destroyed by heat. In these experiments a somewhat violent inflammation, of short duration (two to three days), resulted in the right ears, and a less severe but more prolonged inflammation in the left. An important difference was in the time of onset of this inflammation, which in the previously affected ears appeared many hours earlier than in the others; a difference similar to that which had already been observed to result from the inoculation of living cocci under the same conditions. Thus it appears that parts which have recently suffered from erysipelas become more quickly and intensely inflamed when subjected to the action of the products of the streptococcus than do other parts of the same animal. And when we remember that this tendency to inflammation goes hand in hand with a notably greater resistance to the living microbe, we are led to regard it as beneficial in its action, and an important factor of local immunity; an opinion in harmony with that already expressed by Metchnikoff and others-viz. that inflammation is a protective process.

4. A Form of Experimentally-produced Immunity.

By J. LORRAIN SMITH, M.A., M.D., and E. TREVITHICK, M.B.

The occurrence of fibroid changes in the lungs when these are due to the irritant effect of inhaled dust is, according to clinical authorities, associated with increased liability of the lungs to infection by the tubercle bacillus. On the other hand, there is much clinical as well as experimental evidence to show that the condition of inflammation in the tissues is in general accompanied by an increased power of resisting the invasion of microbes.

The following experiments are brought forward to show that, in its early stages, the inflammation due to irritating dust in the pleural cavity increases the difficulty of infecting the animal in this locality with the bacillus pyocyaneus. The experiments were made on guinea-pigs and rabbits.

The dust (pounded glass) was placed in a bottle containing a quantity of water. This was sterilised, and before injection the dust was stirred up and mixed

with the water. About 1.5 c.c. of this mixture was drawn into the injecting cannula. The cannula consisted of a piece of glass tubing drawn to a sharp point, with a lateral opening a short distance behind the point. This opening was made of a size just sufficient to allow the dust to pass easily through. No force was needed in the injection, the negative pressure due to the inspiratory act being sufficient to suck the moisture into the cavity.

The effects due to the simple dust were observed in several animals of both kinds. These consisted in hyperemia of the lung with exudation of fluid and red cells into the alveolar spaces. There was also exudation of fluid into the pleural cavity in several instances, and it contained usually a considerable number of red cells also. To some extent the epithelium covering, the pleural surface of the lung, was thrown off into the fluid.

The dust was rapidly absorbed into the lymphatic vessels, and could be seen, even after twelve hours, as small round yellowish patches in the pleural membrane. These when examined microscopically were found to contain large numbers of glass particles.

The injection of the bacillus pyocyaneus followed after a time, varying from one to twenty-six days.

In the following table we have a summary of the observations.

Guinea-pigs.-Six animals, with controls:

Two recovered completely.

Three survived the control animals for a period.

One was a contradictory instance, for this died sooner than the control animal.

Rabbits. Seven animals, with controls:

Two recovered, the controls dying on the second day after infection. Three survived the controls in two cases one day, and in one case eight days.

Two cases in which the bacillus was injected into the opposite pleural cavity. One died with the control, the other earlier.

The conclusion which is derived from these experiments is that the early stages of inflammation confer a certain amount of immunity on the pleural cavity in which the inflammation has been set up. It does not seem to vary in its protective power during the first month or so after the inflammation has been set up. In those instances where there was not complete recovery it was usually found that bacilli occurred to a much greater extent in the pleural exudation of the control animals than in that of those infected with glass dust.

The death of the last two rabbits points to the fact that probably the protection conferred is strictly localised in the inflamed tissues.

5. On the Changes in Nerve Cells due to Functional Activity.
By GUSTAV MANN, M.D.

6. On the Effect of Gravity on the Circulation. By Dr. L. HILL.

7. Experimental Inquiry upon the Different Tracts of the Central Nervous System. By F. W. NUTT, M.D.

The origin and termination of the fibres of the fillet were investigated by noting the degeneration resulting from unilateral separation of the nuclei of Goll and Burdach from the arciform fibres issuing therefrom. The degenerated arciform fibres were traced by Marchi's method into the opposite interolivary layer, and thence into the fillet. The degenerated fibres of the fillet were followed mos

distinctly into the optic thalamus, passing through the striae medullares. They could not be traced beyond this to the cortex.

The author also gave a preliminary account of some experiments relating to the antero-lateral tract of Gowers. He considers his researches so far show that it is a crossed tract, consisting in the main of fibres proceeding to the middle lobe of the cerebellum, but also containing a few scattered fibres proceeding from the posterior roots, and apparently ending in the corpora quadrigemina.

MONDAY, AUGUST 13.

The following Papers were read :

1. On the Mechanical Theory of Lymph Formation. By Dr. STARLING.

2. On Lymph Formation. By WALTER S. LAZARUS-BARLOW, M.D.

During the course of experiments performed in the Pathological Laboratory, University of Cambridge, for the investigation of the pathology of the oedema which accompanies passive congestion the author was led to examine certain of the conditions that modify the flow of lymph in the normal animal.

He introduced a cannula into one of the lymphatics of the hind limb of a dog, and, as far as possible, ligatured all remaining lymphatics. The limb was then emptied as completely as possible of lymph by rapid and firm squeezing from the paw upwards, and an observation was immediately commenced upon the amount of lymph formed in the limb during one hour. The animal was under A.C.E. mixture and was kept absolutely at rest, excepting that coagulation of the lymph in the cannula was prevented by occasional gentle squeezing of the limb. Immediately before the expiry of the hour the limb was again emptied of lymph as completely as possibly by firm squeezing. The lymph was collected in carefully graduated tubes, and the amount thus obtained was regarded as the normal for the individual.

An elastic ligature previously arranged round the limb was then tightened to such an extent as, it was known from other experiments, would raise the pressure in the femoral vein from the normal 4-5 mm. of mercury to 25-35 mm. Exactly the same processes were carried out during the collection of lymph under these modified conditions as were described for the normal conditions. The duration of increased pressure was one hour. Lastly, the elastic ligature was removed, and the amount of lymph formed in an hour under normal conditions was again estimated.

The limb was therefore as free as possible from lymph immediately before beginning and immediately before ending each of the three portions of the investigation.

The author found that the amounts collected in the three periods were either absolutely identical, or that the amount collected during the period of high venous pressure was less than that collected when the pressure was normal. On no occasion did he find that an increase of venous pressure was accompanied by an increase in the amount of lymph-flow.

The amount of lymph-flow, however, being the product of two factors-viz. the amount of fluid poured out by the blood-vessels and any modifications in that amount introduced during the sojourn of the lymph in the tissues—it was necessary before concluding that an increase of lymph-formation does not accompany an increase in venous pressure to determine whether an excessive amount of fluid had accumulated in the tissues in the form of oedema, since it was possible that the increased venous pressure might have caused an increased outflow of fluid from the capillaries and venules, and that that increased outflow might not have shown

itself in an increased flow from the lymphatics, because it was in part stored up in the tissues as oedema fluid. To determine this point observations of the specific gravities of arterial blood and blood-plasma, venous blood and blood-plasma, of muscle and of skin were taken before and after the pressure in the femoral vein was raised. It was found that these underwent no changes whatever, either in the affected limb or in other parts of the body (with the exception of a rise in the specific gravity of the venous blood and blood-plasma in the affected limb) during venous obstruction, which caused a rise of pressure in the femoral vein, varying in individual cases from 48-75 mm. of mercury. The modification of specific gravity of the venous blood and blood-plasma in the affected limb manifestly depends upon its lengthened sojourn in the limb.

The author concludes, therefore, that increase of venous pressure in a limb for one hour not only does not cause an increase of lymph-flow from the lymphatics, it does not even cause an increased passage of fluid through the blood-vessel walls. Independently, however, of the venous pressure, the amount of lymph-flow is increased when the tissues have been starved for some time or are overstocked with their own katabolic products.

The following conditions were investigated:

1. Before and after prolonged complete anæmia (three hours), produced by an Esmarch's bandage.

2. Before and after hæmostasis, or complete cutting off of the limb, with whatever blood and lymph it might contain, from the rest of the body by means of a tight elastic bandage for one hour.

3. Before and after stimulation of the sciatic nerve, while the limb was completely anæmic and persistence in situ of the katabolic products, the whole lasting one hour.

All these conditions are followed by arterial dilatation in the part; and, inasmuch as arterial dilatation subsequent to section of the sciatic nerve was found by the author to be unaccompanied by any modification in the amount of lymphflow, he concludes that the increase occurring under the conditions given above is immediately conditioned by the excessive needs of the tissues.

Under extreme conditions, such as those just given, the effect of an increase of venous pressure is markedly different from what it is when such conditions have not been introduced, for now an increase of venous pressure is accompanied by an increase in the lymph-flow, while the lymph-flow diminishes when the venous pressure is again allowed to return to normal. In other words, the lymph-flow now varies directly-the author cannot say whether it be proportionately-with the venous pressure. It now, therefore, bears some resemblance to mechanical filtration. Inasmuch, however, as an obstruction to the outflow of blood from the venous side itself intensifies the necessity of the tissues by damming up in them the waste products they are so anxious to get rid of, this resemblance to mechanical filtration may, after all, be only apparent.

The author concludes, therefore, that lymph-formation does not depend upon purely mechanical conditions of the circulation, but he regards it as dependent upon the needs of the tissues: those needs are, in some as yet unrecognised way, made known to the circulatory apparatus, and lead to variations in the amount of blood-flow through the part, in extreme cases active arterial dilatation of the most marked kind being induced. In such extreme cases, further, the lymph-flow varies directly with the venous pressure, and there is a resemblance to mechanical filtration; but there are reasons for supposing that this resemblance is an apparent and not a real one.

3. On the Innervation of the Portal Vein.
By W. M. BAYLISS and Dr. Starling.

4. On some Vaso-dilator Reflexes. By W. M. BAYLISS.

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