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ADDRESS OF COL. GARRICK MALLERY, U. S. ARMY.

It may be conceded that after man had all his present faculties, he did not choose between the adoption of voice and gesture, and never with those faculties, was in a state where the one was used, to the absolute exclusion of the other. The epoch, however, to which our speculations relate is that in which he had not reached the present symmetric development of his intellect and of his bodily organs, and the inquiry is: Which mode of communication was earliest adopted to his single wants and informed intelligence? With the voice he could imitate distinictively but few sounds of nature, while with gesture he could exhibit actions, motions, positions, forms, dimensions, directions and distances, with their derivations and analogues. It would seem from this unequal division of capacity that oral speech remained rudimentary long after gesture had become an efficient mode of communication. With due allowance for all purely imitative sounds, and for the spontaneous action of vocal organs under excitement, it appears that the connection between ideas and words is only to be explained by a compact between speaker and hearer which supposes the existence of a prior mode of communication. This was probably by gesture. At least we may accept it as a clew leading out of the labyrinth of philological confusion, and regulating the immemorial quest of man's primitive speech.

17742002

1880-1884

How TO OBTAIN THE BRAIN OF THE CAT.

How to obtain the Brain of the Cat, (Wilder).-Correction: Page 158, second column, line 7, "grains," should be "grams;" page 159, near middle of 2nd column, "successily," should be "successively;" page 161, the number of Flower's paper is 3.

17796445

1880-1884

DOLBEAR ON THE NATURE AND CONSTITUTION OF MATTER.

Mr. Dopp desires to make the following correction in his paper in the last issue: "In my article on page 200 of "Science", the expression and should have been and being the velocity of light.

17800472

1880-1884

THE OUTLOOK FOR APPLIED ENTOMOLOGY.

I have thus touched, gentlemen, upon a few of the many subjects that crowd upon the mind for consideration on an occasion like this, - a few gleanings from a field which is passing rich in promise and possibility. It is a field that some of us have cultivated for many years, and yet have only scratched the surface; and, if I have ventured to suggest or admonish, it is with the feeling that my own labors in this field are ere long about to end, and that I may not have another occasion. At no time in the history of the world has there, I trow, been gathered together such a body of devoted and capable workers in applied entomology. It marks an era in our calling, and, looking back at the progress of the past fifteen years, we may well ponder the possibilities of the next fifteen. They will be fruitful of grand results in proportion as we persistently and combinedly pursue the yet unsolved problems, and are not tempted to the immediate presentation of separate facts, which are so innumerable and so easily observed that their very wealth becomes an element of weakness. Epoch-making discoveries result only from this power of following up unswervingly any given problem or any fixed ideal. The kerosene emulsion; the cyclone nozzle; the history of Phylloxera vastatrix, of Phorodon humuli, of Vedalia cardinalis,- are illustrations in point: and, while we may not expect frequent results as striking or of as wide application as these, there is no end of important problems yet to be solved, and from the solution of which we may look for similar beneficial results. Applied entomology is often considered a sordid pursuit; but it only becomes so when the object is sordid. When pursued with unselfish enthusiasm born of the love of investigation and the delight in benefiting our fellow-men, it is inspiring; and there are few pursuits more deservedly so, considering the vast losses to our farmers from insect injury and the pressing need that the distressed husbandman has for every aid that can be given bim. Our work is elevating in its sympathies for the struggles and sufferings of others. Our standard should be high,- the pursuit of knowledge for the advancement of agriculture. No official entomologist should lower it by sordid aims. During the recent political campaign the farmer must have been sorely puzzled to know whether his interests needed protection or not. On the abstract question of tariff protection to his products, we, as entomologists, may no more agree than do the politicians, or than does the farmer himself; but ours is a case of protection from in- jurious insects, and upon that there can nowhere be division of opinion. It is our duty to see that be gets it with as little tax for the means as possible. Gentlemen, I thank you.

17832547

1890-1894

THE VASCULAR CHANGES OF TUBERCULOUS MENINGITIS, ESPECIALLY THE TUBERCULOUS ENDARTERITIES.

1. In tuberculosis meningitis there is a tuberculosis endarteritis characterized by the formation of intimal tubercles and a diffuse subendothelial, intimal proliferation due to implantation of tubercle bacili from the blood. From the endarteritis the infiltration may spread into the muscular coat and the adventitia, and the whole wall may undergo caseous and hyaline degeneration. 2. Tuberculous proliferation in the adventitia may invade the media and the intima, and the whole wall of the arterial segment may undergo degeneration. 3. The veins are constantly the seat of more or less extensive infiltration, which always results from adjacent extravascular or arterial foci. 4. The epithelioid cells of the subendothelial, tuberculous intimal See PDF for Structure proliferation are most likely derived from the subendothelial layer of connective tissue and not from the endothelial lining.

19866790

1895-1899

THE PRODUCTION OF DIPHTHERIA TOXIN.

Toxin of sufficient strength to kill a 400-gramme guinea-pig in three days and a half in a dose of 0.cubic centimetre developed in suitable bouillon, contained in ordinary Erlenmeyer flasks, within a period of twenty-four hours. In such boullon the toxin reached its greatest strength in from four to seven days (0.005 cubic centimetre killing a 500-gramme guinea-pig in three days). This period of time covered that of the greatest growth of the bacilli, as shown both by the appearance of the culture and by the number of colonies developing an agar plates. The bodies of the diphtheria bacili did not at any time contain toxin in cosiderable amounts. The type of growth of the bacili and the rapidity and extent of the production of toxin depended more on the reaction of the bouillon than upon any other single factor. The best results were obtained in bouillon which, after being neutralized to litmus, had about seven cubic centimetres of normal soda solution added to each litre. An excessive amount of either acid or alkali prevented the development of toxin. Strong toxin was produced in bouillon containing peptone ranging from one to ten per cent. The strength of toxin averaged greater in the two and four-per-cent peptone solutions than in the one-percent. When the stage of acid reaction was brief and the degree of acidity probably slight, strong toxin developed while the culture bouillon was still acid; but when the stage of acid reaction was prolonged, little if any toxin was produced until just before the fluid became alkaline. Glucose is deleterious to the growth of the diphtheria bacillus and to the production of toxin when it is present in sufficient amounts to cause by its disintegration too great a degree of acidity in the fluid culture. When the acid resulting from decomposition of glucose is neutralized by the addition of alkali the diphtheria bacilus again grows abundantly. Glucose is not present, at least as a rule, in sufficient amounts in the meat as obtained from the New York butchers to prevent the rapid production of strong toxin if the bouillon is made sufficiently alkaline. In our experiments, when other conditions were similar, the strength of the toxin was in proportion to the virulence and vigour of growth of the bacillus employed.

19866791

1895-1899

THE EFFECT OF ODOURS, IRRITANT VAPOURS, AND MENTAL WORK UPON THE BLOOD FLOW.

The most important of this investigation has been the completion of various improvements in the construction and use of the plethysmograph, by means of which numerous errors attending the use of the instrument have been eliminated. The results of the work show that all olfactory sensations, so far as they produce any effect through the vasomotor system, tend to diminish the volume of the arm, and therefore presumably cause a congestion of the brain. Whenever the stimulation occassions an increase in the volume of the arm, as sometimes happens, it seems to be due to acceleration of the heart rate, which, of course, tends also to increase the supply of blood to the brain. The of odours varies in extent with different individuals, and with the same individual at different times. It was most marked in subjects sensitive to odours. Irritant vapours, such as formic acid, have a marked effect in the same direction-that is, they cause a strong diminution in the volume of the arm. The experiments give no support to the view that pleasant sensations are accompanied by a diminution of the See PDF for Structure blood supply to the brain and unpleasant sensations by the reverse efeect. In all my experiments mental work caused a marked and prolonged diminution in the volume of the arm. This vasomotor effect was sometimes preceded by a transitory increase in the volume of the arm caused by acceleration of heart rate.

19866796

1895-1899

ON THE PIGMENT OF THE NEGRO'S SKIN AND HAIR.

The pigmentary granules of the negro's skin and hair can be freed in several ways from the cells in which they are lodged and collected in any desired amount. As thus obtained, these granules are found to be insoluble in dilute alkalies, dilute hydrochloric acid (hot or cold), alcohol, or other organic solvents when applied in the order named. If, after they have been subjected to the action of dilute hydrochloric acid, they are again treated with dilute alkalies, they are found to give up their pigment, and, on the continued application of heat, the granules dissolve entirely in the alkaline solution, leaving only an insignificant residue. The pigmentary granules are composed of a colourless ground substance or substratum, a pigment, and much inorganic matter. Their inorganic constituents, as thus far determined, are calcium, magnesium, iron, and silicic, phosphoric, and sulphuric acids; and these constituents possibly play an important part in the deposition and fixation of the colouring matter in the granules. The pigment isolated from the granules, and sufficiently freed from adherent inorganic matter, contains only the merest trace of iron-so little, in fact, that we must think of it when entirely pure as free of iron. Heating the isolated pigment with barium hydrate at a temperature of 260 degrees C. entirely frees it from the closely adherent ground substance, and it is then found that the vapours of pyrrol are no longer emitted when it is subjected to dry distillation, and the odour of burnt feathers is no longer discerned, although nitrogen is still present. We can not conclude as the result of our work that the pigment is a derivative of haemoglobin; it seems to us more probable that it is ultimately derived from the proteids of the parenchymatous juices. The total quantity of soluble pigment in the skin of a negro of average size is found to weigh about 1 gramme; the weight of the pigmentary granules is about 3.3 grammes, if we are right in our assumption that they contain sixty-five per cent of water and five per cent of mineral constituents in their natural state in the epidermis. The pigments of the epidermis and hair of the negro are very likely identical. In the present state of our knowledge we can only say that it seems highly probable that the pigment of the negro's hair is not different from the dark pigment found in the hair of the white races, and we may infer that the pigment of the black skin differs only in amount and not in kind from that deposited in the skin of the white man.

19866804

1895-1899

ON HAEMORRHAGIC CYSTS OF THE THYROID GLAND.

1. All the features peculiar to the gross cysts of the thyroid gland which possess fluid contents appear to indicate that they are essentially of haemorrhagic origin. 2. While these gross cysts would seem more especially to occur in glands which already present the features of parenchymatous goitre, the theory of Wölfler that they originate as a consequence of spontaneous rupture of the vesicles is unsatisfactory. 3. It would seem more probable that these large cysts are due to rupture, traumatic or otherwise, of some of the vessels of the organ. The frequent signs of small haemorrhages in cases of parenchymatous goitre without evidence of associated gross change in the surrounding vesicles, the structure of the organ and its exposed position, all appear to favour this view.

19866805

1895-1899

THE INFLUENCE OF ACUTE ALCOHOLISM ON THE NORMAL VITAL RESISTANCE OF RABBITS TO INFECTION.

THE DEDUCTIONS THAT MAY BE DRAWN FROM THE RESULTS OF THESE EXPERIMENTS ARE AS FOLLOWS: That the normal vital resistance of rabbits to infection by streptococcus pyogenes (erysipelatos) is markedly diminished through the influence of alcohol when given daily to the stage of acute intoxication. That a similar, though by no means so conspicuous, diminution of resistance to infection and intoxication by the bacillus coli communis also occurs in rabbits subjected to the same influences. And that, while in alcoholized rabbits inoculated in various ways with staphylococcus pyogenes aureus, individual instances of lowered resistance are observed, still it is impossible to say from these experiments that in general a marked difference is noticed between alcoholized and non-alcoholized animals as regards infection by this particular organism. It is interesting to note that the results of inoculation of alcoholized rabbits with the erysipelas coccus correspond in a way with clinical observations on human beings addicted to the excessive use of alcohol when infected by this organism. In the course of the work an effort was made to determine if, through the oxidation of alcohol in the tissues to acids of the corresponding chemical group, the increase of susceptibility could be referred to a diminution in the alkalinity of the blood as a result of the presence of such acids. The number of experiments thus far made on this point is too small to justify dogmatic statements, but from what we have gathered there is but little evidence in support of this view. Throughout these experiments, with few exceptions, it will be seen that the alcoholized animals not only showed the effects of the inoculations earlier than did the non-alcoholized rabbits, but in the case of the streptococcus inoculations the lesions produced (formation of miliary abscesses) were much more pronounced than are those that usually follow inoculation with this organism. With regard to the predisposing influence of the alcohol, one is constrained to believe that it is in most cases the result of structural alterations consequent upon its direct action on the tissues, though in a number of the animals no such alteration could be made out by macroscopic examination. I am inclined, however, to the belief, in the light of the work of Berkley and of Friedenwald, done under the direction of Prof. Welch, in the Pathological Laboratory of the Johns Hopkina University, that a closer study of the tissues of these animals would have revealed in all of them structural changes of such a nature as to indicate disturbances of important vital functions of sufficient gravity to fully account for the loss of normal resistance. The conspicuous influence of the alcohol on the gastric mucous membrane in many of these animals, with the consequent disturbance of nutrition, is undoubtedly the explanation of the marked loss in body weight that was observed in many of the animals employed in these experiments. In this light the susceptibility induced by alcohol to excess is somewhat analogous to that induced by starvation, where we see the resistance of animals to particular forms of infection very markedly diminished.

19866807

1895-1899

THE HISTOLOGIGAL LESIONS OF ACUTE GLANDERS IN MAN AND OF EXPERIMENTAL GLANDERS IN THE GUINEA-PIG.

The glanders nodule in the class of cases studied by us is in no sense analogous to the miliary tubercle in its histogenesis, and our studies afford no support to Baumgarten's views. The primary effect of the bacillus of glanders on a tissue we found to be not a production of epithelioid cells, which undergo necrosis and invasion by leucocytes, as happens in the cases in which the bacillus of tuberculosis is concerned, but to be the production of primary necrosis of the tissue, followed by inflammatory exudation, often of a suppurative character. Degenerative changes rapidly ensue in the inflammatory products. These conclusions are in harmony with the observations of Tedeschi, above referred to.

19866814

1895-1899

TWO CASES OF SARCOMATOSIS WITH PURPURA HAEMORRHAGICA.

The purpura accompanying the two foregoing cases of sarcoimatosis would seem to find its explanation in the coexistence of several factors, the main feature being an involvement of the vascular system by the sarcomatous elements. There existed in Case I a direct lesion of the vessel wall whereby the sarcoma cells invaded directly the various coats, and were found mainly between the intima and the adventitia, dissecting their way, as it were, along these tracts in the vessel walls. There was further an extensive involvement of the perivascular lymphatics, from which point, indeed, it would seem that the sarcoma cells had invaded the walls of the vessels themselves. In Case II, moreover, not only was there a definite invasion of the lymph spaces near the vessels, but, furthermore, there was undoubted evidence of the existence of emboli of sarcoma cells in the lumina of the blood vessels; and in the immediate vicinity of such conditions haemorrhages were invariably found. While some vessels, and indeed a great many, were quite free from such emboli, in others the lumina were completely occluded by spindle cells, so as to preclude the possibility that these were merely a collection of desquamated endothelial cells, such as is frequently found as the result of post-mortem changes. That such an embolic condition can exist is by no means an unreasonable supposition, and, while it is generally recognised that multiple sarcomata are usually made up of small round cells, in this case we have an undoubted example of sarcomatosis of the spindle-celled variety. There are numerous instances of this " embolic purpura," as it may be called, especially in French and German literature, the condition being associated with rheumatism, valvular lesions of the heart, and other diseases which induce directly or indirectly the formation of emboli. Krauss, Gimard, Leloir, and others have insisted with considerable emphasis on the embolic origin of many purpuric conditions, and in some instances they have verified their observations by histological examination. Leloir assumes that, in addition to the presence of the ordinary emboli and the changes in the vessel walls with desquamative endarteritis, the blood itself may be much altered chemically, and that in the cachectic conditions clots may be thrown down from the circulating blood and be carried onward to form capillary emboli, with resulting haemorrhagic infarctions. Krogerer, some ten years ago, in examining the skin removed from patients with symptomatic purpura, found definite thromboses in the smaller veins, and even in the arteries. According to his view, the alterations in the vessel walls gave rise to slowed circulation and tendency to thrombosis, bringing about a liability to haemorrhages. His plates bear out his theories regarding the thrombi, many of which show considerable organization. But a careful examination of the purpuric areas shows further that a mere invasion of the vascular system by sarcoma cells can not explain all the various blood effusions present. On examining the skin, for instance, in those areas where large irregular haemorrhages had occurred, there was but little evidence of vascular invasion, while the emboli, on the other hand, seemed to exist mainly in the localized smaller and more circumscribed patches. One must therefore conclude that in such instances a combination of factors will alone afford a rational explanation of the purpura, and that in the general condition of the patient we shall find another cause for the enormous effusions of blood. In both of our cases there were high fever, cachexia, and a rapid progressive asthenia, all being the results of a sarcomatosis, and implying also grave alterations in the composition of the blood. From this we may infer an altered condition of the vessel walls, and hence probably a combination of circumstances sufficient to explain the incidence of haemorrhage. The raised cutaneous nodules in our second case, some of which were haemorrhagic, can not be regarded as pure sarcomatous metastases, for on microscopic examination they merely revealed haemorrhage or necrosis, or both, and sometimes plugging of the vessels. There was nowhere in these nodules evidence of new growths. Such elevations, then, must have been produced rather by a temporary serous or cellular exudation coincident with or following upon the haemorrhage-a probability which is emphasized by the fact that during the last days of the patient's illness many of the nodules diminished in size. Whether the oedema and infiltration were secondary to the embolic process in the subcutaneous vessels or whether they were merely coincident with the haemorrhage would be difficult to decide. The ringlike spots, however, are of special interest, inasmuch as it has been shown that they have been present in more than one case of sarcoma. It is not impossible that such spots may be definitely related either to the embolic processes or to a direct invasion of the cutaneous vessels, though, so far as we know, there do not exist any experimental proofs to bear out such a theory. From what has been said, however, it is evident that the cutaneous vessels were plugged during the last few days of the illness, at a time when the walls of the smaller vessels and capillaries were already greatly enfeebled. The result of the embolic formation may therefore mean a decided deficiency in the supply of nutriment to the involved area, the collateral circulation naturally being poor under the circumstances. As soon, then, as the vessels had become plugged, the surrounding blood supply would be poured in to a limited extent, and, on meeting the enfeebled vessels, might possibly break through their thin walls, thus producing a zone of haemorrhage around the area deprived of its normal nutrition. In other words, the condition may be regarded as in many respects analogous to that presented in embolic infarcts in regions with end arteries, central necrosis with peripheral congestion and haemorrhage being induced, the latter being chiefly limited to the outer zone of the necrotic area. The cutaneous vessels under such circumstances may be regarded as end arteries in a functional sense, since the collateral circulation would be so diminished under the altered conditions that no complete nourishment could be afforded to the area supplied normally by the plugged vessel. Von Recklinghausen has directed especial attention to the occurrence of cutaneous haemorrhages following embolic or thrombotic occlusion of peripheral arteries. The possibility of some toxic condition as a factor in the production of the purpura in our cases may also be suggested; but while we would not exclude this possibility, we are unable to find any positive evidence in its favour. Focal necroses, which are often associated with toxic and infectious processes, were present only in direct association with the haemorrhages, and were not distributed in the liver, spleen, and kidneys in the manner characteristic of toxic infections. Nevertheless the absence of these necroses does not exclude the possibility of the existence of some form of toxaemia. Infection demonstrable by bacteriological examination was absent, and there is no reason to regard our cases as allied to the infectious purpuras. The thermic theory suggested by Fagge at all events finds no place in the production of the multiple tumours in our cases, inasmuch as in each instance extensive visceral growths had given rise to the metastases.

19866815

1895-1899

THE REGENERATION OF THE BLOOD.

a. The blood of apparently normal animals undergoes considerable variations within physiological limits. b. After a loss of blood the regeneration is more rapid if there has been a transfusion of an artificial serum. c. Regeneration after transfusion is less rapid during the first half of the regeneration period than during the second half. d. The regenerative processes once stimulated into activity carry the blood, qualitatively, considerably beyond the established normal. (See Plate XXXIII.) Otto (2) observed a similar phenomenon. e. The quantity of haemoglobin per volume of red blood-corpuscles is not constant. f. The volume of red blood-corpuscles varies as the product of the average volume of individual corpuscles and the number of corpuscles per unit volume. (V proportional, variant v x n). g. When the number of the corpuscles increases the size decreases, and conversely, (n proportional, variant(1/2)). h. The quantity of haemoglobin varies in general with the number of red blood-corpuscles per unit volume. (Hb. proportional, variant n).

19866819

1895-1899

A STUDY OF TYPES OF RESPIRATORY MOVEMENTS.

1. Children of the two sexes differ very little in the character of their respiratory movements. 2. Between girls and women and boys and men there is little or no difference in respiratory type. 3. Childbearing does not permanently affect respiration. 4. The natural type of respiration, for both sexes is one in which the movement is fairly equally balanced between chest and abdomen, the abdominal being somewhat in excess. 5. In typical unconstricted individuals the chest contributes about the same bulk of air as does the abdomen. 6. Constricting dress causes preponderance of thoracic movement in ratio to its restriction of abdominal movement and to the sensitiveness of the nervous co-ordination.

19866820

1895-1899

THE IMMUNIZING POWER OF NUCLEOHISTON AND OF HISTON.

THE RESULTS OBTAINED IN THE PRECEDING EXPERIMENTS MAY BE BRIEFLY SUMMARIZED AS FOLLOWS: 1. Nucleohiston does not protect against a separate and subcutaneous injection of tetanus toxin, diphtheria toxin, hog-cholera bacillus, or anthrax bacillus. 2. Mixtures of nucleohiston and either tetanus toxin or diphtheria toxin lose their specific toxic action-the latter much more rapidly than the former. Animals that recover after inoculation of such mixtures are not rendered immune. 3. In a mixture of nucleohiston and anthrax bacillus the latter is unaffected, even after the lapse of eleven days. 4. The destruction of specific toxins in a solution of nucleohiston, though in part due to sodium carbonate, is probably chiefly due to the nucleohiston. 5. Histon does not protect against a separate and subcutaneous injection of tetanus toxin, diphtheria toxin, hog-cholera bacillus, or anthrax bacillus. 6. In a mixture of histon and diphtheria toxin the latter is destroyed in a few minutes. This action is in part, if not wholly, due to the acidity of the histon solution. Similar mixtures of closely related bodies, serum globulin or albumoses, in Witte's pepton, give analogous results. The animals that recover from such inoculations are not rendered immune. Histon does not destroy the tetanus toxin as readily as the diphtheria toxin. 7. Histon possesses decided and marked toxic properties which are not due to the hydrochloric acid present.

19866821

1895-1899

ON THE TIME OF REFLEX WINKING.

I. The mean total time taken from 450 experiments on sixteen subjects was found to be 0.0420 second. II. Natural winks occurring very shortly before the record was taken had no influence. III. The reflex time was found to vary in different individuals, the limits of the mean times being 0.0351 and 0.0491 second. For any given individual there was a close correspondence between averages of sets of experiments obtained under similar conditions. In the case of one man this was true of sets of experiments taken a year apart. Sex has no influence. IV. Apprehension seems to shorten the time.

19866826

1895-1899

A RESEARCH UPON ANAESTHESIA.

THE CONCLUSIONS WHICH HAVE BEEN REACHED BY THE SERIES OF EXPERIMENTS RECORDED IN THE PRESENT MEMOIR ARE: First. Lowered arterial pressure has a comparatively feeble effect upon the respiration, but when the pressure falls sufficiently, respiratory depression does occur. Second. Even excessive lowering of blood pressure primarily stimulates the vaso-motor centre, the sensibility of the centre being evidently necessary to the automatic regulation of the circulation. Third. The circulation recovers itself more slowly after profound etherization than after a like chloroform narcosis. Fourth. It is possible for ether as well as chloroform to produce death some hours after the cessation of its administration, at a time when the cerebrum has long freed itself from distinct evidences of the narcotic, so that consciousness and intellectual action have been restored. In applying these conclusions to the subject of practical anaesthesia it is evident that the depression of the circulation produced by chloroform has effect upon the respiratory centres only when the pressure has fallen very low, and whilst it may be a factor in the production of respiratory failure during chloroformization, the failure must be chiefly due to the direct influence exercised by the drug upon the respiratory centres. Clinical experience shows that nausea and general depression are more pronounced after the use of ether than after the use of chloroform, a difference which is strongly insisted upon by the advocates of chloroform as an important agent in favor of that anaesthetic. Our research confirms clinical observation, and experimentally shows that the depression of the circulation produced by ether is more permanent than that caused by chloroform; the reason probably being the large amount of ether which is necessary to produce profound narcosis, with lowering of the arterial pressure; an amount so large that it can neither be burned up in the system nor yet eliminated in the time which would be necessary for the much smaller amount of chloroform to be gotten rid of after chloroformization.

19866828

1895-1899

EXPERIMENTS ON THE RELATION OF THE INHIBITORY TO THE ACCELERATOR NERVES OF THE HEART.

The experiments described in Part IV of this paper show that in whatever manner the problem of the relation of the vagus to the accelerators is approached, whether the accelerators are stimulated during a stimulation of the vagus, or the vagus during a stimulation of the accelerators, or both are stimulated simultaneously, either for a short or for a longer period, the result is the same, viz., the effect upon the rate of the heart is determined entirely by the relative strength of the stimuli applied to the two nerves. If the stimuli are of approximately the same strength, as judged by the effect of stimulating the nerves separately, the rate of the heart is but slightly affected; if the stimulus applied to the vagus is the stronger, the heart is slowed; if it is weaker, the heart is accelerated. In all cases the result of stimulating the two nerves simultaneously is approximately the algebraic sum of the results of stimulating them separately; sometimes the inhibitory effect slightly predominates, but not more frequently than does the accelerator effect. Moreover, the two nerves may be stimulated simultaneously for a considerable period of time without either completely overcoming the effect of the other. Thus as far as their effect upon the rate of the ventricular beat is concerned, the vagus and accelerator nerves seem to be purely antagonistic; the statement that a minimal stimulation of the one can completely overcome a maximal stimulation of the other is undoubtedly incorrect, and the hypotheses as to the mode of action of these nerves upon the heart, based upon this statement, lose their chief support.

19866829

1895-1899

CHEMISTRY OF COLOSTRUM MILK; A REPORT OF SIX CASES.

Colostrum corpuscles are not always found in so-called colostrum milk; when they are present, the percentage of proteids is higher; as they disappear, the proteid percentage drops. The color of colostrum milk is yellow; this color is especially marked in negroes' milk (observed in four cases not included in this report). The reaction of colostrum milk is alkaline. The specific gravity varies from 1024 to 1034. This variation is chiefly due to the variation in the amount of fat present.

19866832

1895-1899

ON THE ACTION OF SUBSTANCES OF THE DIGITALIS SERIES ON THE CIRCULATION IN MAMMALS.

In summing up the contents of the preceding pages it may be stated that the action of digitalis has been divided into two stages according to the changes evinced by the ventricles under its influence; of these the first is characterized by marked inhibitory action together with modification of the cardiac muscle, while in the second the inhibitory action is less marked and the muscular action becomes the more prominent feature. The inhibitory action is due to direct stimulation by this series of the pneumogastric centrally in the medulla oblongata and peripherally in the heart. The extent to which the inhibitory mechanism is stimulated varies in different animals and with different members of the digitalis series. The muscular action of small quantities betrays itself in a tendency to increase the extent of the contraction, while in some cases the degree of relaxation reached in diastole is also lessened by it. In larger quantities the series increases the irritability of the cardiac muscle very considerably, and the spontaneous rhythm of the ventricles therefore becomes developed. Through the interaction of these two factors in the first stage the rhythm of the whole heart is slowed, the contraction of the ventricle is more complete, and the diastolic relaxation is generally increased, although it may be unchanged or lessened. The systolic pressure is increased and the fall from maximum to minimum pressure is slower than normal owing to the increased completeness and longer duration of systole (Rolleston). The auricles generally contract with less force and may relax more completely than normally. Sometimes, however, their contractions also are more complete than before the injection of the drug. This latter condition generally precedes the diminution of the force of the auricular contraction. This variation of the effects of digitalis in the auricle explains the changes in intra-auricular pressure noted by Kaufmann. The contraction volume of the ventricles is always much increased, and the output per unit of time is generally augmented, and this together with the contraction of the peripheral arterioles causes an increase in the tension in the systemic circulation, an acceleration of the circulation, and possibly a temporary increase in the pressure in the great veins and in the auricle and ventricle in diastole (Kaufmann). The pressure in the pulmonary artery is practically unaffected by some members of the series, while by others it is considerably increased. This difference in the reaction of the pulmonary circulation is due to the varying extent to which these drugs act on the peripheral arteries and not to any difference in their action on the two sides of the heart. If the inhibitory action be very strongly marked the slowing of the heart may be extreme, the ventricles assuming their own spontaneous rhythm and all connection with the auricles being lost. While the contraction volume of the ventricle is still greater than normal, their output per unit of time may become less than normal, the aortic tension therefore fall and the rapidity of the circulation be lessened. The ventricles maintain their association throughout, and probably the rhythm of the two auricles also remains equal. The ventricular rhythm, however, becomes irregular owing to the variation in the duration of the diastolic pause. The auricles may cease altogether in diastole, or may continue to beat with a slower or faster rhythm than the ventricles. During the second stage the rhythm of the heart becomes accelerated owing to the increased irritability of the heart muscle. The ventricle tends to assume a rapid spontaneous rhythm, while the auricular rhythm is also quicker than in the first stage. When these two rhythms interfere by the passage of impulses across the auriculo-ventricular boundary in either direction, irregularity of the heart is produced, generally bearing a distinctly periodic character. The ventricles continue to maintain their common rhythm, while the auricles and ventricles may contract at quite different rates. The two ventricles, however, do not necessarily contract with equal force, and the contractions of one may present periodic variations in strength, while those of the other may be almost perfectly uniform. The contractions of the auricles vary in the same way as regards each other and the ventricles. The inhibitory nerves are no longer able to slow the ventricular rhythm, but may affect the completeness of systole and diastole in the ordinary way. The auricular contractions can still be lessened in force and possibly be abolished by their stimulation, and the impulses passing between the auricle and ventricle may therefore be blocked and regularity of the heart produced by powerful inhibition. The irregularity of the contractions is therefore due indirectly to the increased irritability of the cardiac muscle and the acceleration must be attributed to the same cause. An extreme phase of this stage produced by the interference of the rhythms is a temporary standstill of one of the chambers, generally the auricle. The irregularity leads to a lessened efficiency of the work of the heart. The output varies extremely in successive observations and the contraction volume of every individual beat may differ. The various chambers often show a tendency to dilate during this stage. The blood pressure in the systemic arteries at first remains high, in fact may be higher than in the first stage owing to the increased rapidity of the heart rhythm, but afterwards falls continuously as the periodic variations become shorter in duration. The auricles generally cease contracting before the ventricles, but not invariably. There is no fixed order in the cessation of the ventricles or auricles. Each division comes to a standstill in a position somewhat nearer diastole than systole and then passes into delirium and dilates to the fullest extent.

19866833

1895-1899

A GRAPHIC STUDY OF TREMOR.

FROM OUR OBSERVATIONS I THINK THE FOLLOWING PROPOSITIONS ARE JUSTIFIED: (1) All muscular movements are made up of a series of elementarycontractions and relaxations in alternation, which may be appreciable as tremor in conditions of both health and disease. (2) The differences between different tremors are of degree rather than of kind, i. e. no one form of tremor is distinctive of any one disease or group of diseases. (3) No definite relation exists between one form of tremor and any other. (4) The frequency of movement is in inverse ratio to the amplitnde and vice versâ. (5) Habitual movements are performed with greater freedom from tremor than unusual movements. (6) There is no material difference between the movements of the two sides of the body, except as related to Proposition (5).

19866834

1895-1899

NODULAR FORMS OF TUBAL DISEASE.

THE CONCLUSIONS AT WHICH WE ARRIVE ARE THE FOLLOWING: 1. Nodular enlargement of the tube can be caused by a number of different pathological conditions. 2. Clinical examination does not enable us to make a diagnosis of the pathological condition existing in an individual case of nodule of the tube. 3. The diagnosis of the nature of a tubal nodule can be made only with the microscope. 4. The conditions causing nodular enlargement of the tube are congenital or acquired, non-inflammatory or inflammatory. 5. Any one of these conditions can exist without the production of nodules. 6. The nodules can be found in all parts of the tube and-taking the peculiar anatomy of each part of the tube into account-show the same structure. 7. The enlargement can be caused by epithelial or epithelioid formations, connective or muscular tissue, by round-cell infiltrations or combinations of two or more of these. 8. The epithelial formations originate in the epithelium of a. the tubal mucous membrane (salpingitis pseudo-follicularis, adenomyoma originating in the tubal epithelium). b. the accessory tubes (intraparietal parasalpinx and hydro-parasalpinx). c. remnants of the Wolffian body (adenomyoma). 9. The epithelioid formations originate in the peritoneal endothelium (peritoneal growths under "relative heterotopy"). 10. The excess of formation of connective tissue is a consequence of inflammatory conditions of the tubal wall (salpingitis interstitialis, Zweifel). 11. The hypertrophy of the muscular tissue is a. non-inflammatory (adenomyoma). b. consequent upon inflammation-Kaltenbach's case (23). 12. The accumulations of round cells are direct evidence of inflammation: a. non-specific (salpingitis interstitialis disseminata, salpingitis abscedens); or b. specific (salpingitis tuberculosa or s. gonorrhoica). 13. The epithelioid formations can occur wherever pseudo-membranes cover organs lined with a serous coat. 14. Extra-uterine pregnancy (abdominal or tubal) produces epithelioid formations by causing pseudo-membranes to form-not by any irritation peculiar to the pregnancy.

19866836

1895-1899

ON THE CAUSE OF THE HEART BEAT.

1. The cause of the rhythmic contraction of the ventricle lies within the ventricle itself. 2. The cause of the rhythmic contraction is not a single, localized, co-ordination centre; the co-ordination mechanism, whatever it may be, is present in all parts of the ventricle. 3. The integrity of the whole ventricle is not essential to the coordinated contractions of a part of the ventricle. 4. The apex of the mammalian heart possesses spontaneous, rhythmic contractility. 5. Assuming that the general belief in the absence of nerve cells from the apical part of the ventricle is correct, these experiments demonstrate that nerve cells are not essential to spontaneous, long-continued, co-ordinated contractions of the ventricle.

19866837

1895-1899

ON THE APPEARANCE OF CERTAIN AMOEBOID BODIES IN THE BLOOD OF VACCINATED MONKEYS (RHOESUS) AND CHILDREN, AND IN THE BLOOD FROM CASES OF VARIOLA: AN EXPERIMENTAL STUDY.

1. The claim of L. Pfeiffer that small granular amoeboid bodies are present in the blood of vaccinated children and calves, and in the blood from cases of variola, during the stage of fever is confirmed. A nucleus has not been positively made out in any of these bodies. 2. Granular amoeboid bodies, having a diameter about one-third that of a red blood cell, appear, also, in the blood of the monkey during the active stage of vaccinia and disappear with the decline of the local inflammation. 3. A body of like appearance, granulation and size may occasionally be found in the normal blood of monkeys and children. 4. Pale amoeboid bodies, containing a few dark pigment-like granules, are present in the blood from cases of variola and in the blood of the variolated monkey. Bodies of like appearance may occasionally be found in the blood of vaccinated children and monkeys.

19866847

1895-1899

THE INFLUENCE OF ENVIRONMENT UPON THE BIOLOGICAL PROCESSES OF THE VARIOUS MEMBERS OF THE COLON GROUP OF BACILLI: AN EXPERIMENTAL STUDY.

Assuming the typical colon bacillus and the typical typhoid bacillus to represent the types of this group that present the greatest divergences in biological peculiarities, we conclude, as others also have done, that there is a series of closely related forms that may be regarded as intermediate or transitional and which serve to establish a biological relationship, either near or remote, between these two typical members. From our own studies we are inclined to regard the typical colon bacillus as the type of this group, for the reason that its functional equilibrium, as observed in the intestine, is so permanent a quality that it may readily be perpetuated under what is ordinarily regarded as favorable artificial circumstances, and that with the continuance of such conditions there is no conspicuous tendency on the part of this organism to deviate from what we regard as its norm; whereas, on the other hand, with all the other members of this group with which we have worked, there is not only a lack of uniformity in the adjustment of the functions, but such as exists is readily disturbed under artificial environment; though it must be borne in mind that even with the typical colon bacillus we have also shown functional modifications to be possible under particular conditions. When the members of the colon group are cultivated under circumstances favorable to the development of both the function of fermentation and that of proteolysis, fermentation invariably takes precedence and no evidence of proteolysis is manifested until after fermentation has ceased. The cultivation of all the members of the colon group under circumstances that favor the development of one function, viz. that of proteolysis, at the expense of another, viz. that of fermentation, results first in an apparent increase of vigor; but this is of temporary duration and is quickly followed by the decline and death of the cell. The result of this increased activity of the proteolytic function is the formation of much larger amounts of indol by typical colon cultures than has ever been obtained by us by any other method. By the method of experimentation through which we were enabled to accentuate the proteolytic activity of the typical colon bacillus, as caused by an increase of indol formation, we have also induced the function of indol formation not only in atypical colon bacilli that had been devoid of it, but in every specimen of typical typhoid bacilli to which we had access as well. We feel justified in regarding one of the differential tests between the typhoid and colon bacillus, namely that of indol formation on the part of the latter and the absence of this function from the former, as of questionable value, for the reason, as shown above, that by particular methods of cultivation indol production has been shown to accompany the development of a number of specimens that we have every reason to regard as genuine typhoid bacilli. As a result of our own experiments, together with the observations of others, there can be no doubt that the bacillus coli communis at times possesses pathogenic properties, and that by artificial methods of treatment it may often be brought from a condition of benignity to one of virulence. The spleen of a typhoid patient has always been regarded as the only trustworthy source from which to obtain the typical typhoid bacillus. While we believe this to be true, still our investigations show that other members of the colon group may also be present in this viscus; in fact, from such spleens we have isolated practically all of the varieties of this group with which we are acquainted. From our experience, the value of the serum test for the differentiation of typhoid and colon bacilli would seem to be questionable. We are inclined, however, to attribute the irregularities recorded above as due more to the method of application than to defects of the principles involved; for, as stated, by the use of dried blood, as in our experiments, it is not possible to make the test with constant and accurate, or even approximately accurate, dilutions of the serum. Our irregularities may be in part due to this defect. We therefore lay less stress upon this than upon the other features of our work.

19866851

1895-1899

A STUDY OF THE ACTION OF ACONITIN ON THE MAMMALIAN HEART AND CIRCULATION.

The action of aconitin on the dog's heart, therefore, seems to consist in: 1. A stimulation of the inhibitory mechanism, especially of the centres in the medulla oblongata. 2. An increase in the irritability of the muscle of the auricle and the ventricle, which leads to independent contractions of one or both of these divisions and culminates in fibrillary contractions in the ventricle. The first of these is the only effect seen in the therapeutic use of the drug, and aconitin may, therefore, be considered to be indicated when it is desirable to stimulate the inhibitory centre without acting on the heart muscle. Of course it has a further effect on the circulation through the stimulation of the vaso-motor centre, but this would appear to be of minor importance.

19866852

1895-1899

A CONTRIBUTION TO THE STUDY OF HUMAN NEUROGLIA.

THE RESULTS AND CONCLUSIONS OF THE ABOVE INVESTIGATION ARE: 1. The term glio-sarcoma should be dropped, as unscientific and misleading in its significance. 2. The problems regarding neuroglia demand varied methods for their adequate study. 3. With all the means at our command, the absolute determination of the relation of cells and fibres in individual cases remains difficult and at times impossible. 4. No criterion has yet been offered to determine a fundamental distinction between glioma and sarcoma (Stroebe); and secondly, between glioma and so-called gliosis (Weigert). 5. The development of neuroglia in all probability is from cells with protoplasmic processes to cells with differentiated and independent fibres. 6. Herein lies a possible reconciliation of the conflicting views concerning the ultimate structure of human neuroglia.

19866854

1895-1899

FOCAL OR INSULAR NECROSIS PRODUCED BY THE BACILLUS OF TUBERCULOSIS.

1. It must be accepted from a comparison between the histological changes described in the focal necroses due to abrin and ricin, diphtheria, eclampsia, blood-serum intoxication, typhoid fever, lobar pneumonia and glanders, and those described here in three cases of tuberculosis, that the last are also instances of focal necrosis. 2. It may be claimed that the areas of necrosis in the three cases of tuberculosis had their origin in ischaemia, for the reason that they were numerous in the spleen and were not found in the kidney. Against such an explanation of their causation are the facts: that other forms of necrosis affect frequently the spleen and seldom the kidney; that thrombosis of vessels or any fixed relation of the areas in the spleen to blood-vessels could not be established; that the tubercle bacilli were invariably present; and lastly and of no slight importance, that these necroses were all present in cases of marked marasmus. 3. That the areas of necrosis in these three cases might be phenomena resulting from a mixed infection with pyogenic bacteria is possible, but no groups, colonies or even single bodies could be found which answered to the requirements in shape or staining properties for such bacteria. Even were it the case that the focal necroses here presented are the histological lesions of a septicaemia occurring as a complication of tuberculosis, the presence of the bacillus of tuberculosis in the areas of necrosis would still require explanation. 4. Lastly, it is not unreasonable to suppose that a diminished resistance on the part of the tissues incidental to marasmus is an important factor in the production of these necrotic lesions.

19866856

1895-1899

ON A METHOD OF ISOLATING AND IDENTIFYING BACILLUS TYPHOSUS, BASED ON A STUDY OF BACILLUS TYPHOSUS AND MEMBERS OF THE COLON GROUP IN SEMI-SOLID CULTURE MEDIA.

Semi-solid culture media, and more especially media rendered semi-solid by temperatures of from 30 degrees to 40 degrees C., seem to have an important bearing in the differentiation of bacterial species, particularly those presenting various degrees of motility. In such media not only the effect of differences in consistence on the motility of an organism may be noted, but the effect produced by various chemicals and nutrient ingredients on the growth and motility may be readily observed. By systematically varying the constituents of such media it has been possible to produce a medium in which the behavior of Bacillus typhosus differentiates it from the various members of the colon group; and also to produce a medium in which the colonies of Bacillus typhosus assume a form which distinguishes them from the colonies of the colon bacilli in plate cultures. Bacillus typhosus alone of all the organisms investigated during these experiments has displayed both the power of giving rise to thread-forming colonies in the plating medium and that of the uniform clouding of the tube medium, hence these two characters may prove to be of great value in the identification of this organism. The practical application of the use of these media has led to the ready detection of Bacillus typhosus and its isolation from the stools of patients suffering from typhoid fever. No suspected water has been subjected to test, but from the investigation of artificially infected tap-water the media here described may be assumed to have an application in the detection of Bacillus typhosus in such waters.

19866858

1895-1899

PRELIMINARY OBSERVATIONS ON A CASE OF PHYSIOLOGICAL ALBUMINURIA.

1. The proteids consisted of albumins and globulins, varying in quantity between the extremes of.9010 grm. and.2592 grm. in the 24 hours, but usually between.7 and.37 grm., the average being.5317 grm. 2. The quantity of the proteids varies directly as the urea, inversely as the external temperature. The relation between the quantity of urine and the quantity of proteid is not constant. The quantity of the proteida is little affected by diuretics; it tends to be increased by certain drugs that act upon the circulation. It is lessened during sleep. It is apt to suffer a sudden temporary increase, returning as suddenly to the usual average. For this phenomenon we have no explanation. 3. From.5449 to.6616 grm. of coagulable proteids a day may be excreted through the urine for an indefinite time by an otherwise healthy individual without damage to either kidneys or organism.

19866865

1895-1899

THE FATE OF THE GIANT CELLS IN HEALING TUBERCULOUS TISSUE, AS OBSERVED IN A CASE OF HEALING TUBERCULOUS MENINGITIS.

From the foregoing description of the histological changes in the leptomeninx it is quite evident that we are dealing with a chronic, stationary, healing form of tuberculous inflammation. This statement is substantiated, in the first place, by the clinical history. The only reasonable interpretation of the symptoms would establish the duration of the process as four months. The imaginable contingency that there existed first a meningeal syphilitic lesion that was dispersed by the iodide of potassium only to be followed by a tuberculous infection is so remote and unlikely that it need not be discussed. At all events the tuberculous leptomeningitis, which presented a typical distribution, began insidiously, existed at times in a latent condition, and pursued a very anomalous course, marked by a relative mildness of all the symptoms, and thus it came about that when an apparent or real improvement followed the administration of iodide of potassium able observers were induced to make an erroneous diagnosis. Death occurred as a result of an intercurrent infection. The long duration of the process is also shown, anatomically, by the thick layer of firm, translucent and gelatinous material that matted together the structures at the base, and also by the evident adhesions between the pia and the brain. The histological examination furnishes proof positive of the correctness of the conclusion in regard to the peculiar character of this process because it shows: (1) That the tuberculous proliferation is uniform in development and has reached nearly the same stage of evolution throughout the entire extent of the leptomeninx involved; it is not a process that has advanced by exacerbations and irregular extensions; the lesions are, generally speaking, of nearly the same age everywhere and must have begun at about the same time. (2) That only a very limited degree of caseous degeneration is present, pointing to an early arrest of the activity of the tubercle bacillus or to a very decided diminution or attenuation of its virulence. (3) That the subendothelial intimal proliferations of epithelioid cells, so generally found in acute tuberculous leptomeningitis,* have in this case become more or less completely changed into distinct fibrous tissue in which but very slight, if any, direct evidence of its tuberculous origin can be found. It is only by recognizing that the chronic endarteritis is most marked in correspondence with the most advanced adventitial tuberculous changes, and by finding an imperfect, much altered giant cell in one district of intimal thickening, that we were able to establish the direct kinship of the endovascular changes with those of the pia in general. (4) That acute inflammatory changes, in the form of emigration of polymorphonuclear leucocytes and of fibrinous exudation, are entirely absent in all parts of the district involved. The presence of a turbid serous fluid is of course not at all inconsistent with the view that the anatomical changes are of long duration. (5) That the granulation tissue present is, in general, undergoing fibrillation and contains a rich supply of enabryonal capillary vessels as well as of larger blood-vessels of evidently new formation. The absence of any considerable extent of polymorphonuclear leucocytic infiltration in this tissue has already been referred to. The cells in the granulation tissue correspond to the cells of embryonal or formative connective tissue. Vacuolation is rarely present. (6) That the unusually large number of giant cells present are remarkably free from evidences of necrosis and degeneration of the character ordinarily observed in tuberculous proliferations, that they do not contain in demonstrable form tubercle bacilli, and that the majority of the giant cells seem to be separating into individual cells and smaller masses often with, but sometimes also without, evidences of nuclear disintegration. The possibility that these phenomena may signify fusion instead of the sundering of cells will be discussed below. For these reasons there can be no doubt that the general claim that we are dealing with an instance of chronic, healing tuberculous meningitis must be regarded as established beyond dispute. The growth of tubercle bacilli in the glycerine-agar tubes, inoculated with the fluid from the pial meshes, and the demonstration of tubercle bacilli, though in very small numbers, between the cells of the embryonal tissue, furnish the positive evidence that we are actually dealing with a tuberculous process due to living and not to dead bacilli. The degree of virulence of the cultures of tubercle bacilli was, unfortunately perhaps, not studied. The presence of living tubercle bacilli in a tissue free from active and acute changes characteristic of tuberculosis demonstrates that, whatever the actual degree of virulence of the bacilli may have been, the tissue in which they were found was at this time relatively immune from their action. The manner in which this immunity was produced, and in which the process of healing was initiated, need not be discussed at this time any further than to again direct attention to the fact that the bacilli lost their virulency as regards the cells in this leptomeninx before these cells underwent any marked degree of degeneration. The cells of the tuberculous proliferations survived the further action of the bacilli whose original effect it was to initiate cell accumulation or proliferation; the cells also retained sufficient vitality to develop, in some instances at any rate, into formative cells according as their origin would dictate, e. g. into fibroblasts. That fibroblasts are formed only by embryonal connective tissue cells, and not by wandering cells, such as the large mononuclear leucocytes, we are well aware, is possibly still a disputable assumption, and we do not consider it pertinent to discuss the question any further in connection with this study, but would only emphasize the point that some of the cells of tuberculous proliferations may, under favorable circumstances, become formative cells, and, furthermore, that the amount of formative tissue produced may be far in excess of what is actually needed for purposes of repair only. Surely the appearances here noted indicate that the bacillus of tuberculosis has the power to stimulate fixed cells to multiply, unless one assumes that all, or almost all, the formative cells here seen are derived from wandering cells attracted by the presence of the bacillus and its products. As to the ultimate fate of the formative and other cells in this healing tuberculous tissue no final statements can be made. It must be remembered that it is only one stage in the process of healing that is dealt with. The well marked evidences of fibrillation, the quite extensive formation of new vessels, the absence of evidences of degenerative changes in the uninuclear cells, all point to the production of new fibrous tissue as sure to occur, but it seems quite probable that occasional epithelioid cells may undergo or have undergone dropsical or other forms of degeneration, although it is certainly apparent that so far as the small cells are concerned the involution of the tuberculous tissue is not occurring through disintegration. Perhaps the most interesting feature in this case is the opportunity it affords to study the changes in the giant cells of healing, non-degenerated tuberculous tissue. In the first place, the large number of giant cells is quite remarkable. The general characters of the tissue in which they are found recall the fact that giant cells are regarded as quite constant elements in chronic mild tuberculosis; often the giant cells are the only cells that contain bacilli (Koch). In this instance the giant cells do not contain bacilli that are demonstrable by the usual methods; neither do they contain bodies that can be definitely interpreted as degenerate forms of bacilli such as those found by Metchnikoff, Stchastny, Weicker, and others, in the giant cells of Spermophilus guttatus, in avian and in human tuberculosis. Metchnikoff states, however, that he knows of the occurrence of such degenerate forms only in the Spermophilus guttatus under the circumstances mentioned, and in the rabbit and guinea-pig in mammalian tuberculosis, but not in man; consequently, the manner in which the giant cells rid themselves of the bacilli undoubtedly present in their interior at some time during their existence, must as yet remain without any explanation. In the description of the histological changes the various appearances presented by the giant cells are described somewhat minutely. The essential observations made concern, in my opinion, the further fate of giant cells which are still found to persist in healing nondegenerated tuberculous tissue. It was, I believe, quite conclusively shown that the consecutive changes appear to consist in the breaking up of the nuclei, the removal of the detritus by phagocytes, and the formation of a few apparently viable uninuclear cells in the case of more degenerated, exhausted giant cells, while other, and, as it would seem, better preserved or younger giant cells, separate into a number of individual, uninuclear cells with but little or no nuclear disintegration. Objection might be raised to this interpretation of the appearances in the giant cells. While no one could very well dispute the view that part of the giant cells are undergoing retrogressive and absorptive changes with the production of some viable cells, a question might well be raised concerning the nature of the process taking place in those giant cells that have been spoken of as splitting up or dividing into uninuclear cells and smaller multinucleated masses without much evidence of nuclear disintegration. (ABSTRACT TRUNCATED).

19866866

1895-1899

A CASE OF PSEUDO-LUPUS VULGARIS CAUSED BY A BLASTOMYCES.

The case reported, in this article is one of a somewhat extensive cutaneous disease, which occurred in a man, 33 years of age, who gave the following history: The disease first made its appearance, eleven and a half years ago, at the back of the left ear, as a pimple which soon became pustular. The process extended forward, very slowly and gradually encroached upon and covered almost the entire face, the central portion of which now presents an atrophic cicatricial condition. Another similar lesion occurred, one month after the primary invasion, on the back of the hand, which healed in about four years, after treatment with caustic. A third lesion appeared on the right side of the scrotum (six months after), which increased in size for a year and then healed spontaneously. A fourth inoculation appeared, on the anterior surface of the left thigh just above the internal condyle, and grew for a year, after which it gradually healed spontaneously. A fifth lesion appeared on the back of the neck and also healed spontaneously after growing for a year. The disease when first examined presented many of the features of a lupus vulgaris. There were no enlarged lymphatic glands and the patient's health had always been good. The family and personal history revealed no syphilitic or tuberculous taint. Sections from the cutaneous lesions showed the presence of what appeared to be budding blastomycetes. The sections also presented pathological features similar to those seen in the first case recorded by Gilchrist; in many sections almost typical tubercles were found. The organisms in the tissue are chiefly spherical, unicellular bodies varying from 10-20 micro in diameter, and consist of a doubly contoured membrane, which encloses a fine granular protoplasm with sometimes a vacuole. Many budding forms in various stages were found; nonucleus could be demonstrated, neither were any mycelium or hyphae present in the tissues. The parasites were almost always found outside of cells, comparatively few being enclosed in giant cells. Pure cultures of the organism were obtained directly from the cutaneous lesions in two places from the pus squeezed out from between the papillomatous variety of the lesion. The organism grew on all ordinary media, and especially well on potato and beer-wort agar. The cultures showed both budding forms and a fairly profuse mycelium. Older cultures, carried through many generations, produced sometimes little or no mycelium. The organisms in the cultures were round, ovoid, doubly contoured, refractive bodies, varying in size from about 10 to 20micro in diameter. The mycelium was, on rare occasions, of two varieties, very fine and also coarse with sessile buds and conidia. Dogs, a horse, a sheep and guinea-pigs were successfully inoculated, the most striking results being nodules, grossly simulating tumors, in the lungs. Microscopically these nodules were of a chronic inflammatory nature and contained numerous parasites identical in appearance with those in the patient. In the tissues of none of the animals successfully inoculated was any mycelium found. Since our organism did not ferment sugar and produced in cultures mycelium, it may either belong to the blastomycetes or to the oidia, but in conformity with prevailing nomenclature we regard it as a blastomyces. We shall term the disease which has been produced by this organism Blastomycetic Dermatitis. We give the name Blastomyces dermatitidis to the parasite which we have isolated and described in this paper. In closing we are of the opinion that it would be advisable to examine more carefully all tuberculous lesions of the skin, and especially those of tuberculosis verrucosa cutis, for the presence of blastomycetes. This can be readily and rapidly done by soaking the unstained sections in ordinary liquor potassse, when the organisms if present will stand out as doubly contoured refractive bodies.

19866867

1895-1899

EXPERIMENTAL THYROIDISM.

FROM THE RESULTS OF THE VARIOUS EXPERIMENTS ALREADY DETAILED I FEEL JUSTIFIED IN DRAWING THE FOLLOWING CONCLUSIONS: (1) Absolutely fresh thyroid gland is not poisonous, in the usual sense of the term, when absorbed through the alimentary canal. (2) The symptoms of induced thyroidism are manifestations of an intoxication resulting from the ingestion of decomposed thyroid material, a conclusion that agrees in part with the previously related observations of Lanz. (3) The so-called experimental thyroidism is not specific for the thyroid only, for the ingestion of many substances derived from animal tissues other than the thyroid gland may produce an intoxication strikingly similar in every respect to that of experimental thyroidism. (4) Most, if not all, animal tissues yield substances which, if injected in large quantities directly into the circulation or beneath the skin, will produce an intoxication often very similar to that produced by injections of various substances derived from the fresh thyroid tissue. (5) The effects resulting from the intravascular or subcutaneous injections of aqueous extracts, decoctions and the concentrated extractives of the thyroid tissue, of the thymus, of muscle, etc., are by no means necessarily indicative of the function and the action of the hypothetical internal secretions of the same tissues during life. (6) The utilization of the fact that ingestion of decomposed thyroid material produces on certain occasions an intoxication with certain symptoms similar to some of those of G-raves' disease is not justifiable for the furtherance of the theory that the symptoms of exophthalmic goitre result from an over-production of the thyroid secretion. (7) Our results lead us to conclude with Drechsel that the fresh thyroid tissue yields at least probably two substances that are capable of palliating the symptoms of the acute cachexia in totally thyroidless dogs. (8) The thymus tissue also yields one and probably two substances that are as equally capable as the thyroid extractives of palliating the acute cachexia in totally thyroidless dogs. (9) Neither of the above substances is an enzyme, nor does either contain iodine. (10) Neither the feeding of minced raw thyroid glands, nor the injection of aqueous thyroid extracts, decoctions, and concentrated solutions of the extracted palliative thyroid principles is capable of keeping totally thyroidless young dogs alive longer than a few weeks (possibly three weeks). Still less capable are the thyroid preparations containing decomposition products. (11) The presence of one, or usually several, small accessory thyroid bodies, which gradually hypertrophy and wholly or partially assume the functions of the excised thyroid lobes, accounts for the occasionally long survival of thyroidectomized, thyroid-fed, young dogs. (12) Totally thyroidless young dogs are so quickly overwhelmed by the cachexia, and the intervals between the thyroidectomy and the onset of the severe dyspnoeic attacks and subsequent deaths differ so slightly, no matter which of the usual varieties of fresh food are employed, that kinds of fresh food cannot be unquestionably affirmed to influence the onset of the cachexia in any especially definite manner. Animal foods, in which constituents poisonous to rabbits have developed, probably slightly hasten the onset of the severer symptoms, and the vaunted remarkably modifying influence of a diet of ordinary milk, such as Breisacher observed, does not exist in the case of the totally thyroidless dog. (13) Monkeys whose general metabolism is disturbed in consequence of the removal of a greater portion of the thyroid gland, evidently become more susceptible to those constituents of meat that are poisonous to rabbits, and sufficient clinical evidence exists for concluding that probably a like susceptibility to animal foods containing such constituents also exists in men when the function of the thyroid gland is sufficiently disturbed. (14) And, finally, as regards the thyroid factor in the pathology of exophthalmic goitre, I agree with Gley that the majority of the symptoms in many patients with that disease can apparently, from an experimental standpoint, be as plausibly explained by the hypothesis of partially deficient thyroid activity as by the hypothesis of augmentation of thyroid function.

19866869

1895-1899

AN EXPERIMENTAL STUDY OF FAT STARVATION WITH ESPECIAL REFERENCE TO THE PRODUCTION OF SEROUS ATROPHY OF FAT.

THE FOLLOWING INFERENCES MAY BE MADE FROM THE FOREGOING STUDY: 1. The lesions resulting from fat starvation, at least in the case of pigs, do not resemble or even suggest those of rickets. 2. Prolonged fat starvation leads to the entire disappearance of fat from the adipose tissues. The form of fat atrophy observed as the result of experimental fat starvation corresponds to the serous fat atrophy described by Flemming, and is essentially the same type of fat atrophy as that found in the epicardial and perirenal fat in the human subject as the result of wasting disease. 3. The. lecithins of the brain and the fat of the liver are not materially reduced by fat starvation. 4. Fat starvation does not lead to advanced serous fat atrophy of the subcutaneous fat if the animal be given a large excess of carbohydrate food or a considerable excess of the carbohydrate and proteid constituents of milk. 5. Fat starvation causes a very imperfect absorption of the salts of P(2)O(5) from the intestine.

19866873

1895-1899

STUDIES ON TRICHINOSIS, WITH ESPECIAL REFERENCE TO THE INCREASE OF THE EOSINOPHILIC CELLS IN THE BLOOD AND MUSCLE, THE ORIGIN OF THESE CELLS AND THEIR DIAGNOSTIC IMPORTANCE.

TO SUMMARIZE, WE HAVE BEEN ABLE TO DEMONSTRATE: (1) In a case of acute trichinosis an extensive leucocytosis, with great absolute and relative increase in the number of eosinophilic cells in the blood, associated with a coincident decrease in the quantity of neutrophilic elements. (2) From the examination of specimens of muscle removed during life, besides the peculiar degenerations of the muscle, a longitudinal splitting of some of the fibres; a remarkable transverse splitting of others; a great proliferation of nuclei, about many of which vacuoles are seen; and large numbers of polymorphonuclear eosinophilic cells, which are especially prevalent in the more degenerated areas. (3) In a second case (after death), besides similar changes in the muscle, large numbers of eosinophiles throughout the infested portion. (4) In two other cases, during life, a great increase of the eosinophilic cells in the blood, with a coincident decrease of the polymorphonuclear neutrophiles, associated with leucocytosis, though of less extent than in the first case. (5) In pieces of muscle removed in these last two cases changes in most respects similar to those cited in the first case, but of less degree. (6) The similar character of the nuclei of the eosinophiles and the neutrophiles both in the blood and in the muscle, and the presence in the first case of certain cells which might be regarded as forms transitional between neutrophiles and eosinophiles, suggesting the possibility that the increase in the latter elements may, in these instances, take place in the muscles by direct transition from the neutrophiles.

19866874

1895-1899

ON THE PRESENCE OF THE TYPHOID BACILLUS IN THE URINE.

Typhoid bacilli were demonstrated in the urines of 9 out of 38 typhoid patients (about 25 per cent). 172 specimens were examined with 44 positive results. (2) The bacilli, when demonstrated, were always present in large numbers and in practically pure culture. (3) The bacilli appeared first in the later stages of the disease and persisted in the great majority of cases far into convalescence. The urines of typhoid patients should, therefore, not only be rigidly disinfected during the disease, but they should also be carefully supervised during convalescence. (4) The typhoid bacilli were practically always associated with albuminuria and the presence of renal casts. On the other hand urines containing considerable amounts of albumin and casts in large numbers often showed no typhoid bacilli. (5) Irrigation of the bladder with antiseptic solutions offers a possible means for removing permanently the bacilli from the urine.

19866875

1895-1899

THE FATE OF THE GIANT CELLS WHICH FORM IN THE ABSORPTION OF COAGULATED BLOOD SERUM IN THE ANTERIOR CHAMBER OF THE RABBIT'S EYE.

The conclusion seems warranted that the giant cells formed in the absorption of coagulated blood serum inserted into the anterior chamber of the rabbit's eye subdivide again into uninuclear small cells that take part with other new-formed cells derived from the lining of this space to form a densely fibrillated mass of tissue that resembles quite closely the cornea in its structure. This demonstration materially strengthens the opinion expressed by the writer in his previous article in this Journal,* that the giant cells in healing non-degenerated tuberculous tissue may separate into small living cells, and that the giant cells of tuberculosis are not necrobiotic elements from the very moment and from the very mode of their formation, as has been the general teaching, especially in Germany.

19866880

1895-1899

A HISTOLOGICAL STUDY OF TYPHOID FEVER.

The typhoid bacillus produces a mild diffusible toxine, partly within the intestinal tract, partly within the blood and organs of the body. This toxine produces proliferation of endothelial cells which acquire for a certain length of time malignant properties. The new-formed cells are epithelioid in character, have irregular, lightly staining, eccentrically situated nuclei, abundant, sharply defined, acidophilic protoplasm, and are characterized by marked phagocytic properties. These phagocytic cells are produced most abundantly along the line of absorption from the intestinal tract, both in the lymphatic apparatus and in the blood-vessels. They are also produced by distribution of the toxine through the general circulation, in greatest numbers where the circulation is slowest. Finally, they are produced all over the body in the lymphatic spaces and vessels by absorption of the toxine eliminated from the blood-vessels. The swelling of the intestinal lymphoid tissue of the mesenteric lymph nodes, and of the spleen is due almost entirely to the formation of phagocytic cells. The necrosis of the intestinal lymphoid tissue is accidental in nature and is caused through occlusion of the veins and capillaries by fibrinous thrombi, which owe their origin to degeneration of phagocytic cells beneath the lining endothelium of the vessels. Two varieties of focal lesions occur in the liver: one consists of the formation of phagocytic cells in the lymph spaces and vessels around the portal vessels under the action of the toxine absorbed by the lymphatics; the other is due to obstruction of liver capillaries by phagocytic cells derived in small part from the lining endothelium of the liver capillaries, but chiefly by embolism through the portal circulation of cells originating from the endothelium of the blood-vessels of the intestine and spleen. The liver cells lying between the occluded capillaries undergo necrosis and disappear. Later the foci of cells degenerate and fibrin forms between them. Invasion with polymorphonuclear leucocytes is rare. Many of the phagocytic cells pass through the liver and lungs, and get into the general circulation. A few come from the abdominal lymphatics through the thoracic duct.

19866884

1895-1899

NOTES UPON AN EPIDEMIC OF FOWL CHOLERA AND UPON THE COMPARATIVE PRODUCTION OF ACID BY ALLIED BACTERIA.

. The bacillus isolated by me from the outbreak of choleraic diarrhoea corresponds closely in all essential particulars with that of European chicken cholera. (b). It differs, consequently, from that isolated from previous outbreaks of choleraic diarrhoea in the United States. (c). A study of the acid production by this and allied bacilli would seem to show that the amount of acid produced by so variable a microbe varies greatly and is incapable of affording a further means of distinguishing between allied forms.

19866887

1895-1899

ACUTE INTERSTITIAL NEPHRITIS.

Acute interstitial nephritis is found in the infectious diseases of children, particularly in diphtheria and scarlet fever, but may be met with in other infectious diseases. The disease is characterized by general and focal infiltration of the interstitial tissue of the kidney with cells which correspond to those which Unna has described under the name of plasma cells. The focal character of the infiltration is marked; even in the cases in which all parts of the kidney show some interstitial cellular infiltration the cells are most abundant in certain foci. These foci are found in three places: in the boundary zone of the pyramids, in the sub-capsular region of the cortex, and around the glomeruli. A considerable number of cases is found in which the blood-vessels of the boundary zone of the pyramids contain nnmbers of lymphoid and plasma cells without any infiltration of the interstitial tissue. The new cells in the interstitial tissue are due to emigration from the blood-vessels and multiplication by mitotic division of the cells which have emigrated. The cells can emigrate as plasma. cells or as lymphoid cells, and the latter may change into plasma cells in the tissues. In the normal individual, plasma cells may be formed in the mucous membrane of the intestine, where they practically form the entire tissue between the epithelium and the muscularis mucosa, and to a limited extent in the spleen. In diphtheria, in scarlet fever, and probably in a number of infectious diseases, plasma cells are formed in great numbers in the spleen and bone-marrow, and to some extent in the lymphatic glands. In the spleen they are formed from the cells of the Malpighian bodies, which are often principally composed of them, and to some extent from the cells in the pulp. They are formed from the lymphoid cells. No adequate explanation is found for the focal character of the lesions in the kidneys. There is some ground for believing that the physical conditions of the circulation may have something to do with their accumulation in the vessels in certain places. It is also possible that in the interstitial foci there may be soluble substances which exert a positive chemotaxis for them. Such substances may be foundin the urine, which may exert its influence on the interstitial tissue in different places. The explanation of the foci cannot be found in primary focal degeneration of the epithelium. Epithclial degeneration in these cases is always present, but it is diffuse. In foci where it is more intense and due to the interstitial changes, polynuclear leucocytes are found in the tissue, in the degenerated epithellum and in the tubules. Folynuclear lencocytes and not plasma cells are attracted by degenerated tissue. The foci are not due in these cases to the local action of bacteria. In a number of the cases in which interstitial nephritis was found the kidneys were shown to be sterile both by cultures and by microscopical examination. In cases where bacteria were present they were found only in small numbers in cultures and not on microscopical examination, and their connection with the foci could not be demonstrated. In three cases plasma cells were found in the interstitial tissue in definite bacterial diseases of the kidney. In these cases they were not found in connection with the lesions produced directly by the bacteria, but in the periphery of the purulent foci.

19866889

1895-1899

THE RELATION OF THE TOXICITY OF DIPHTHERIA TOXIN TO ITS NEUTRALIZING VALUE UPON ANTITOXIN AT DIFFERENT STAGES IN THE GROWTH OF CULTURE.

Until recently diphtheria " toxin " was supposed to be a single definite substance and to have a definite toxicity in animals and neutralizing power for antitoxin. A fatal dose of toxin, without regard to the conditions under which it was produced or preserved, was supposed to require always the same quantity of antitoxin to neutralize it. Ehrlich's researches have completely done away with this theory, and have substituted for it one which assumes the toxin to be only at its origin a single definite chemical compound with definite physiological and antitoxic properties. According to Ehrlich the toxin is an unstable substance which readily loses its toxicity, while at the same time its affinity for antitoxin may be either increased or decreased. Its neutralization by antitoxin he considers to be due to a chemical union between the toxin and the antitoxin. The results of our experiments as detailed in this paper are fully in accord with those published by Ehrlich, as to the varying neutralizing value of a minimal fatal dose of " toxin "; they, however, go further and indicate roughly a general law in accordance with which these changes occur. The neutralizing value of a fatal dose of toxin is at its lowest in the culture fluid when the first considerable amounts of toxin have been produced. After a short period, during which the quantity of toxin in the fluid is increasing, the neutralizing value of the fatal dose begins to increase, at first rapidly, then more slowly. While the culture is still in vigorous growth and new toxin is being produced, the neutralizing value of the fatal dose fluctuates somewhat, but with a generally upward tendency. After the cessation of toxin production the neutralizing value of the fatal dose increases steadily until it becomes five to ten times its original amount. In our experiments the greatest value for L(+) was 126, the least 27. As at 6 hours L(+) was only 72 and at 28 hours only 91, we doubt whether L(+) ever reaches above 150, and therefore hardly expect Ehrlich's figures of 200 to be realized. When we seek to analyze the above-described process, we find certain facts which seem partly to explain it. Experiments have shown that filtered toxin, preserved for any length of time in conditions under which access of air occurs, gradually loses in both its toxicity and neutralizing power, and that it loses more rapidly in the former property than in the later. Thus, while the fatal dose of a toxin preserved for one year rose from.01 cc. to.55 cc., it lost only half as much in neutralizing value, one unit neutralizing at first 1 cc., at the end of the year 25 cc. These processes take place more rapidly at room temperature than in the ice chest, and in the incubator than in the room. In the fluid holding the living bacilli we have, therefore, after the first few hours of toxin formation, a double process going on, one of deterioration in the toxin already accumulated, which tends to increase the neutralizing value of the fatal dose, the other of new toxin formation, which probably tends to diminish the neutralizing value. The chemical changes produced by the growth of the bacilli in the bouillon tend to aid one or the other of these processes and so to make from hour to hour slight changes in the value of the fatal dose. Later, with the period of cessation of toxin production, the gradual deterioration of the toxicity alone continues, and the fatal dose gradually and steadily increases in its neutralizing value. Ehrlich's theories, as to the splitting up of " toxin " into toxoids having little or no toxicity but on the average full neutralizing power for antitoxin, have not in our opinion been substantiated by the results of these experiments. The difference between the amount of toxin mixed with a unit of antitoxin which causes the first symptoms and that causing death upon the fourth day would be, it is true, explained by his theory, but the failure of this difference to be greater where, by his theories, epitoxoids should be in great abundance prevents our acceptance of his views. The fact of the greater neutralization value of a fatal dose of a deteriorated toxin would be accounted for on his protoxoid theory. This, however, is not proof of its correctness, as other theories, such as the production by the diphtheria bacillus of two or more closely allied toxins, similar to the allied alkaloids produced by plants, would equally account for it, if we supposed the one which had the greater neutralization value was more resistant to destruction than the other. We only advance this theory to call attention to the fact that many theories can on paper explain a process without necessarily being thereby established. Even if his theories prove partially correct, we feel certain that his formula for standardizing toxins is founded upon error and cannot be employed for the purpose intended by him. While we do not believe, therefore, that he has changed the principles of testing antitoxin, yet we believe he has contributed greatly to uniformity in results by calling attention to the necessity of selecting a suitable toxin and by employing and distributing an antitoxin as a standard to test toxins by. In this way smaller testing stations can make their results correspond with those of the central station. In spite of the great variations in the neutralizing value of a fatal dose in different toxins, we do not believe there has been any such great difference in the toxins used by the different stations for testing purposes. Most laboratories have taken the culture fluid at about the time of its greatest toxicity, and the neutralizing value of a fatal dose of this toxin would seldom vary more than 10 per cent above or below the standard now adopted in Germany by the government testing station, this latter being presumably as close as possible to that used to establish the original Behring-EhrIich unit. Where error has been made, it has usually been by taking too old culture fluids, which would cause the antitoxin strength of samples tested to be estimated below and not above its real value. Culture 8, which is used not only by us but by many other laboratories in the United States and Europe, fortunately produces on the 6th day, the time at which the culture is usually removed, a toxin which grades Elirlich's antitoxin within five per cent of the strength given by him. We believe that by using such a bacillus, we can, after gaining a fuller knowledge of its characteristics, obtain a toxin of a known and suitable neutralizing value, and thus always correctly standardize an antitoxic serum. Meanwhile a fairly permanent antitoxin, such as Ehrlich provides, is of immense value in insuring a uniform though not necessarily correct standard among the different testing stations and in allowing of comparison between them.

19866893

1895-1899

AN EXPERIMENTAL STUDY OF THE DIRECT INOCULATION OF BACTERIA INTO THE SPLEEN OF LIVING ANIMALS; AND A CONTRIBUTION TO THE KNOWLEDGE OF THE IMPORTANCE OF A LESION IN ANIMAL TISSUE FOR THE LODGMENT AND MULTIPLICATION OF BACTERIA WITHIN IT.

I. Cultures of B. coli communis, B. typhosus and Staph. pyogenes aureus, when injected into the tissue of the normal spleen, soon disappear from that organ, and indeed from the normal body generally. II. Bacteria injected into a spleen after the whole or a part of the vessels have been tied, multiply in the spleen with great rapidity and continue to supply bacteria to the blood, whence in the healthy body they soon disappear. III. Bacteria injected into the spleen, or subcutaneous tissue, or into the blood current through the ear vein, in cases in which moderate lesions have been made by cauterization or compression in the spleen, liver, kidney, uterus, testicle, peritoneum, or subcutaneous tissue, usually find lodgment in these lesions and multiply there. IV. Even in cases in which numerous foci existed, from which the blood was constantly provided with a fresh supply of bacteria, only few bacteria were found at any time in the blood.

19866894

1895-1899

ON THE PRESENCE OF CHOLIN AND NEURIN IN THE INTESTINAL CANAL DURING ITS COMPLETE OBSTRUCTION: A RESEARCH ON AUTOINTOXICATION.

My experiments lead me to believe that complete occlusion of the small intestine at its lower end will give rise to the occurrence of cholin, neurin and perhaps other bases, provided the food taken contains any considerable quantity of lecithin. It is not improbable that still other poisons are formed by bacterial action from other constituents of the food in cases of intestinal obstruction. While cholin would have to be absorbed in relatively large amounts to exert a marked toxic action in human beings it is otherwise with neurin, which is many times more intense in its action and must be classed with the exceedingly active poisons. It has been shown both by the experiments of Schmidt and Weiss and also by those recorded in this paper that the poisonous neurin may be formed from cholin by bacteria. In its physiological action neurin agrees closely with muscarin; especially to be noted here is the paralytic action on the heart and its power to increase the intestinal movements to such an extent that continual evacuations occur. Whether the ptomaine which was found by me is poisonous 1 cannot yet say. It must be considered proved, however, that highly toxic substances may arise in the intestinal canal during its complete occlusion. The method of treating cases of intestinal obstruction, before surgical means are resorted to, namely, washing out the stomach and as much of the gut as possible often reduces the violent paristalsis and this is due, perhaps, to the removal of substances out of which irritating and toxic products are formed by bacteria. In conclusion, I would remark that our knowledge of the fate of lecithin in the digestive canal under normal conditions is very deficient. The assumption that it is saponified by the fat-splitting enzyme of the pancreatic juice, thus yielding cholin, glycero-phosphoric acid and fatty acids, rests on the work of Bókai in 1877 and, as that investigator himself admits, without excluding bacterial action. This omission throws grave doubts on the results. If the assumption of Bókai be correct, caution must be observed in the use of some foods that have been considered most nutritious and healthful; for instance, the ingestion of a meal made up largely of eggs would hardly be without danger because of the poisonous action of the large quantity of cholin liberated from the lecithin and the probability of the formation of the highly poisonous neurin. It is my purpose in the near future to examine this question with the help of modern methods.

19866895

1895-1899

GLYCOSURIA IN DIPHTHERIA.

There is a transitory glycosuria in diphtheria, which is found frequently in the severe cases and is usually present in the fatal ones. (2) This glycosuria is often associated with albuminuria. (3) Injections of diphtheria antitoxin are occasionally followed for a few days by a slight glycosuria.

19866898

1895-1899

ACTION OF FORMALDEHYDE ON ENZYMES AND ON CERTAIN PBOTEIDS.

THE FOLLOWING GENERAL CONCLUSIONS MAY BE DRAWN FROM THE PRECEDING WORK: Fibrin is altered by formaldehyde and is then less easily digested by pepsin and by trypsin. Papaïn is apparently unable to digest fibrin even when this is exposed to very weak formaldehyde for a very short time. The casein of milk, on contact with formaldehyde, undergoes rapid alteration and is as a result not coagulated by rennet, or but very slowly. Such altered casein, like similar fibrin, is not readily digested by the proteolytic ferments. The longer the formaldehyde acts on casein and on fibrin the more marked is the result. Pepsin is not affected by a one per cent solution of formaldehyde, even when the mixture has stood for four weeks. Even a five per cent solution of formaldehyde acting for three weeks has no effect on pepsin. Contrary results obtained by others are due to an alteration of the fibrin by the formaldehyde. A putrid solution of pepsin in distilled water one month old digests fibrin as readily as a fresh solution. Rennet is not affected even by a four per cent solution of formaldehyde acting for several weeks. The absence of coagulation at times is due to the action of formaldehyde on the casein of the milk and not on the rennet ferment. Papaïn is very quickly altered by formaldehyde, even in very dilute solution. Moreover, it is unable to digest fibrin that has been exposed to the action of a very dilute solution of formaldehyde for a short time. Trypsin is altered by formaldehyde to such an extent that digestion of fibrin will not take place, or but very slowly. The extent to which trypsin is affected by formaldehyde depends largely upon the amount of organic matter present, as well as on the amount of ferment in the solution. Amylopsin is not destroyed by very dilute solutions of formaldehyde, but stronger solutions decrease the activity of the ferment, and if used in sufficient concentration will destroy it completely. Ptyalin, like the diastatic ferment of the pancreas, is not destroyed by dilute solutions of formaldehyde. If the latter is used in rather strong concentration and allowed to act for some time it will destroy the ferment. The action of formaldehyde is more rapid and more marked at a slightly elevated temperature than at ordinary room temperature. Malt diastase, unlike the diastatic ferments of the saliva and pancreatic solution, is not destroyed by formaldehyde when this is used in moderate amount and at ordinary temperature. Unlike pepsin, a solution of malt diastase readily undergoes decomposition on standing even for one or more days. This destruction is undoubtedly due to bacteria since it does not take place when formaldehyde is present. Consequently the favoring action which formaldehyde apparently exerts on diastase really consists in the inhibition of the growth of micro-organisms, and hence the diastase is protected against decomposition.

19866901

1895-1899

A SECOND CASE OF GONORRHOEAL SEPTICAEMIA AND ULCERATIVE ENDOCARDITIS WITH OBSERVATIONS UPON THE CARDIAC COMPLICATIONS OF GONORRHOEA.

An acute gonorrhoeal urethritis may be the starting point for a grave general septicaemia with all its possible complications. (2) These infections may be mixed or secondary, due to the entrance into the circulation of organisms other than the gonococcus, or they may be purely gonococcal in nature. (3) Endocarditis is an occasional complication of gonorrhoea. (4) This endocarditis may be transient, disappearing with but few apparent results, or it may leave the patient with a chronic valvular lesion, or it may pursue a rapidly fatal course with the symptoms of acute ulcerative endocarditis. (5) The endocarditis associated with gonorrhoea is commonly due to the direct action of the gonococcus, hut may be the result of a secondary or mixed infection. (6) Pericarditis may also occur as a complication of gonorrhoea, but it is less frequent than endocarditis. It may, as in the case of the latter, be the result either of a pure gonococcal or of a mixed infection. (7) Grave myocardial changes, necroses, purulent infiltration, embolic abscesses are common in the severe gonococcal septicaemias. (8) In instances of gonococcal septicaemia the diagnosis may, in some cases, be made during life by cultures taken from the circulating blood according to proper methods.

19866902

1895-1899

REPORT OF EXPERIMENTAL WORK ON THE DILUTION METHOD OF IMMUNIZATION FROM RABIES.

1. I have simplified the dilution method by using a stock glycerine emulsion of the virulent cord, from which the desired dilutions can be readily prepared. The proportion of glycerine should not exceed (1/5) part, if it is desired to retain the full virulence of the emulsion. 2. There is some danger of giving rabies to animals in the dilution immunization treatment, a danger which is not present in the Pasteur method. 3. The dried-cord method does not rest solely upon the principle of dilution, but is based also upon attenuation of the virus. 4. The Pasteur method being entirely free from the element of danger which pertains to the glycerine dilution method and resting upon a sounder experimental basis is the one to be preferred.

19866905

1895-1899

A STUDY OF THE SPINAL CORD BY NISSL'S METHOD IN TYPHOID FEVER AND IN EXPERIMENTAL INFECTION WITH THE TYPHOID BACILLUS.

The application of the Nissl method to the study of the motor cells of the spinal cord, and the nerve cells of the dorsal root ganglia in typhoid fever, shows that these cells regularly suffer pathological changes in the course of the infection. (2) The alterations in the motor cells are more constant and of a severer grade than are those in the cells of the sensory ganglia. The more characteristic changes consist of disintegration, solution and destruction of the chromatic substance of the cell starting from the axone hillock and proceeding toward the nucleus. Coincidently the nuclei of the affected cells seek the periphery. Alterations are also suffered by the nucleus and nucleolus. (3) While this central form of ehromatolysis is the prevailing type of pathological change, disintegration, etc., of the Nissl bodies situated in the periphery of the cell and in the dendrites is also observed (peripheral chromatolysis). (4) In experimental infection with typhoid bacilli in rabbits a similar series of lesions in the corresponding nerve cells in the spinal cord and ganglia is encountered. (5) The main or central type of lesions discovered is identical with that found in man and animals after section, destruction, or even slight injury of the peripheral nerves. (6) The examination of the peripheral nerves arising from the lumbar segment of the cord (the site in man and rabbit of the most profound changes) in rabbits inoculated with typhoid bacilli showed well-marked evidences of parenchymatous degeneration. (7> It is probable that lesions of the peripheral nerves in typhoid fever in human beings are common and that the post-typhoid hyper sthesias and paralyses are due to this cause. (8) Restitution of the chromatic granules may take place in the affected nerve cells, the new formation beginning about the nucleus and extending through the protoplasm.

19866906

1895-1899

THE THERMAL DEATH-POINT OF TUBERCLE BACILLI IN MILK AND SOME OTHER FLUIDS.

1. Tubercle bacilli when suspended in. distilled water, normal salt solution, bouillon and milk, are destroyed at 60 degrees C. in 15 to 20 minutes. The larger number are destroyed in 5 to 10 minutes. 2. When tubercle bacilli are suspended in milk, the pellicle which forms during the exposure at 60 degrees C. may contain living bacilli after 60 minutes.

19866907

1895-1899

A CASE OF HAEMOCHROMATOSIS.-THE RELATION OF HAEMOCHROMATOSIS TO BRONZED DIABETES.

There exists a distinct morbid entity, haemochromatosis, characterized by the widespread deposition of an iron-containing pigment in certain cells and an associated formation of iron-free pigments in a variety of localities in which pigment is found in moderate amount under physiological conditions. (2) With the pigment accumulation there is degeneration and death of the containing cells and consequent interstitial inflammation, notably of the liver and pancreas, which become the seat of inflammatory changes accompanied by hypertrophy of the organ. (3) When chronic interstitial pancreatitis has reached a certain grade of intensity diabetes ensues and is the terminal event in the disease.

19866911

1895-1899

THE RELATION OF DEXTROSE TO THE PRODUCTION OF TOXIN IN BOUILLON CULTURES OF THE DIPHTHERIA BACILLUS.

1. Dextrose is not in itself injurious but rather favorable to toxin production. When added in quantities not exceeding 0.2 per cent to peptone bouillon freed from fermentable acid-producing substances (muscle sugar) it leads to a maximum accumulation of toxin by utilizing the available peptone to the best advantage. 2. The different courses taken by cultures of diphtheria bacilli in ordinary unfermented peptone bouillon containing muscle sugar and in peptone bouillon made from fermented infusion to which 0.1 to 0.2 per cent dextrose has been added are manifested by an increased production of toxin in the latter as well as by a rapid return from an acid to an alkaline reaction. In the former an acid reaction may prevail even under most favorable conditions. 3. These differences may be explained by assuming either that the acid products of the muscle sugar are different from those of dextrose and non-utilizable, or else that the bouillon contains certain other unknown inhibitory substances removed during fermentation. The use of synthesized media and an analysis of the acid products in fermented bouillon plus dextrose and in unfermented bouillon would aid in explaining the differences. 4. Among the accessory conditions which favor the toxin production in unfermented bouillon, as pointed out by Park and Williams, are increased quantities of peptone, well developed surface growth of the diphtheria bacilli, and a low initial acid reaction (phenolphthalein). In fermented bouillon these accessory conditions are also favoring, though of legs importance.

19866915

1895-1899

THE ORIGIN OF FAT FROM PROTEIN IN THE SO-CALLED FATTY METAMORPHOSIS OF PHOSPHORUS POISONING.

588.780 grm. of frogs, all of the same sex, of the same comparative approximate weights, taken from the ground about the same time, kept awake and without food for nearly the same time, were divided into equal groups; the one group was poisoned with phosphorus, the other group held as a control. The frogs in the poisoned group lost in dried residue 8.821 grm. or 16.5 per cent of the dried residue of the control group; 1.182 grm. of nitrogen, corresponding to 7.388 of proteid, or 18.45 per cent of the nitrogen and protein in the control frogs; 1.026 grm. of fat, or 22.64 per cent of the fat in the control animals; and 0.261 grm. glycogen, or 13.3 + per cent of the glycogen in the control frogs. I believe that it is obvious that in these experiments no fats were produced from protein. Mathematically, it is possible to conceive that fats could have been formed but entirely burned up. As previously stated, the carbon in the proteid lost during the poisoning was equivalent to 4.600 grm. of fat, and it is conceivable that these 4.600 grm. of fat were formed, but that they, together with the 1.026 grm. of fat actually lost during the experiments, were burned. In brief, the fat combustion might have been tremendously increased, and masked an actual fat formation. This however is unsupported by evidence, and is highly improbable. It is hard to conceive that in an organism whose katabolic functions were greatly augmented as the result of phosphorus poisoning, in which protein, fat, and glycogen were being burned in excess, the carbon of the protein would first have been converted into fat and then the fat burned as such. I believe the only conclusion which can be drawn from these experiments is that no fat was formed as the result of phosphorus poisoning. Thus the fatty degenerations so-called which occurred in these frogs did not comprehend any formation of fat at all, but simply the deposition of fat. These results are directly opposite to those of Polimanti. Polimanti apparently did not weigh his animals before the beginning of the experiment, and based his calculations upon the relation of the fat to the dried residue. Obviously his calculation was based upon the assumption that the dried residue of a frog was unaffected by phosphorus poisoning. Polimanti, in declining to base his calculations upon the weight of the animals when dead, states that as water is often increased, such a calculation would be misleading. But since the dried residue may and does vary, calculations based upon it are also misleading, and thus the only proper basis of calculation is the original weight of the frogs before the experimentation. Calculated upon the basis of the dried residue, in my material the percentage of fat in the control animals was 8.48 per cent, in the poisoned animals 7.86 per cent, so that, even upon the basis of Polimanti's incorrect calculation, in my experiments fat was lost in notable quantity. Just before this study was completed, the publication of Athanasiu, (8) from Pflueger's laboratory, appeared. Operating with a large number of frogs, and under varying conditions, with careful methods and rigid controls, Athanasiu reached the conclusions: that phosphorus poisoning has no effect upon the total quantity of fat in frogs; that it has little effect upon the nitrogen; that it produces a diminution in the quantity of glycogen; and that the fatty degenerations are really fatty infiltrations. While my results agree with those of Athanasiu in the essential point, that no fat was produced by phosphorus poisoning, they differ in that the poisoned frogs, in my experiments, lost fat and protein as well as glycogen, while his frogs lost only glycogen. Since our methods were almost the same, the differences must have resided either in the conditions surrounding the experiments, or in the animals. I do not believe that such differences exist between the Rana fusca and esculenta of Europe and the Rana palustris of America as to explain the differences in our results. These differences I believe may be explained by varying conditions. My animals were kept in a warm cellar, at a temperature of from 18 to 20 degrees C. The period of poisoning with Athanasiu's frogs varied from one to six days; all of my frogs lived over six days, most of them ten or twelve days. Since we know that the katabolic actions of most poisons are greater in prolonged intoxications, it is fair to assume that the time element was the factor in the production of my results. While it would be unscientific and illogical to state that fat cannot be formed from protein, the fact stands that it has never been shown, either in physiology or pathology, that fats are formed from protein. On the contrary, nearly all of the careful work upon the question has yielded negative results. Not. only has it never been shown that, in fatty degeneration so-called, fat is formed from the cellular protein, but it has never been demonstrated that fat is then formed at all, even from glucosides, etc., substances from which fats may be readily formed.

19866916

1895-1899

CULTURES FROM THE BLOOD In SEPTICAEMIA, PNEUMONIA, MENINGITIS AND CHRONIC DISEASES.

OUR CONCLUSIONS FROM THE LITERATURE AND OUR OWN EXPERIMENTS MAY BE SUMMARIZED AS FOLLOWS: I. Blood for bacteriological examination during life should be taken directly from the veins and in considerable quantity. II. Resorption of toxines is the most important feature in cases of sepsis; pyogenie bacteria invade the general circulation in a rather small proportion even of severe eases, and, as a rule, late in the course of the disease. III. A general infection by the pnenmococcus can be demonstrated occasionally in the late stages of acute lobar pneumonia. IV. The value of blood cultures as a means of diagnosis in obscure cases of sepsis is limited by the fact that invasion of the blood by the specific organism cannot be demonstrated during life in the majority of cases. Positive cultures are very valuable; negative cultures do not exclude local septic infections. V. The detection of specific bacteria in the blood of cases of sepsis and of pneumonia gives a very unfavorable prognosis in most cases. VI. General terminal infections with pyogenic cocci occasionally occur as an immediate cause of death in chronic disease. Local infections processes play this part more frequently. VII. As far as our experiments have shown, invasion of the blood by bacteria during the death agony, with subsequent distribution of the genus to the organs by the circulation, is a rather uncommon occurrence. VIII. Owing to the relative infrequency of agonal invasion, we believe that in the majority of cases where the autopsy is performed promptly after death, the bacteria which are found in the organs succeeded in reaching these organs previously to the death agony, and are associated with the course of the disease. IX. The presence of bacteria in the organs of late autopsies is due in many cases to post-mortem extension from one organ to another, and in some cases to the post-mortem growth of small numbers of genus which were distributed to the organs by means of the circulation.

19866918

1895-1899

AN EXPERIMENTAL INVESTIGATION OF THE TREATMENT OF WOUNDS OF THE HEART BY MEANS OF SUTURE OF THE HEART MUSCLE.

It would, of course, be incorrect to attempt to draw conclusions as to the dangers and the chances of success of suture of cardiac wounds in man from the results obtained by animal experimentation. Animals are placed in very unfavorable conditions after the operation. They are very restless and cannot be kept quiet. Ideal cleanliness is impossible and the animals may infect their wound by rubbing the external wound against the dirt on the floor of their cage. From the animal mortality in these investigations no rigid inferences applicable to human beings can therefore be made. Some conclusions of importance can, however, be drawn. Above all, my experiments seem to show that the mammalian heart will bear a much greater amount of manipulation than has hitherto been suspected. Very large wounds of the heart can heal and the healing process occurs in a manner entirely analogous to that in other muscular tissues. Even an extensive suture of the heart-wall of rabbits and dogs, although we know that thereby a large number of muscle fibres are destroyed and replaced by connective tissue, does not interfere with the function of the cardiac muscle as a whole. Can some of the results in the above recorded experiments be, with some restrictions of course, applied to the human heart? I think that this question must be answered in the affirmative. If we compare the knowledge we possess of wounds of the heart in man, with that obtained from animal experiments, and find that they agree in all essential particulars, then we are justified in reasoning by analogy that suture of wounds of the heart in man will give results similar to those obtained in the animal. In the last few decades, the advances made in all the branches of medicine-especially in pathology, bacteriology and surgery-have been due to a great extent to the generalization of the results of animal experimentation. To the careful and critical investigator, the results obtained in the animal experiment have always been of the greatest value in indicating to him the possibility of results to be obtained by similar procedures in the human body. From the study of wounds of the heart in man, and from the results obtained in my experiments, this conclusion seems therefore justified: wounds of the heart in man, when all other means have been tried and found wanting, can and ought to be closed by suture. The application itself of the suture is devoid of the one great danger that was feared in the past, i. e. of sudden arrest of the heart during the manipulations incident upon the application of the sutures. The number of sutures should be as small as possible so as to limit the amount of connective tissue which will be formed; for all the muscle fibres that are compressed by the sutures eventually atrophy and are replaced by new-formed connective tissue. It is probable that this connective tissue will not lead to degenerative changes in the heart-muscle. On the post-mortem table, fibrous plaques are often found in the otherwise normal human heart. In a number of the muscles of the body fibrous bands-tendinous intersections as they are called-are normally found. In the large number of microscopic sections of the heart-muscle that I have examined, I could find no evidence of pathological changes in the muscle fibres some distance from the scar. For similar reasons the suture should always be an interrupted one. We have shown that there are dangers and disadvantages in the continuous suture both on theoretical grounds and in practical use. The sutures should be passed through as little of the heart substance as possible; if they penetrate the epicardium and a small part of the thickness of the heart-muscle it will generally be sufficient. When the heart's action is not too rapid, each suture should be tied during a diastolic relaxation of the part under treatment. On this point we have not yet any experience in man. Cappelen, in his patient, tied the sutures during systole. Rehn tied them in his case during diastole. Only time and further experience will show how much importance is to be attached to this point. All that can be said, in the present state of our knowledge, is, that on theoretical grounds and from animal experimentation, it must be considered safest to tie the sutures during diastole. On first sight, it might appear difficult to apply sutures to an organ in such constant motion as is the heart. In practice, however, the difficulties have been proven not to be so great as might appear. The heart may be grasped with a forceps and the needle and suture easily passed. It is no more difficult to pass and tie a suture in a large dog than in a small rabbit. Hence we should infer that the difficulties of this procedure in the human heart, are not so great, a fact that has been borne out by the experience of those surgeons who have reported cases of heart-suture in man. The cases will always be few in which this extreme method of treatment-for so we must style it-is necessary. Indeed, of the patients that come under the care of the surgeon, there are some who will recover from even large heart wounds without any local treatment at all. Cases have been recently reported by Conner, Brugnoli, Hamilton and others, where after wounds as large as three centimetres, the haemorrhage ceased spontaneously and the patients recovered. One cannot say, therefore, that wounds larger than a certain size must always be sutured. Each case must be carefully considered by itself. When we examine the nine cases of suture of the human heart in man (see pages 487 to 490) we cannot but hope for considerable success from this new method of surgical procedure. Of the nine cases, four recovered entirely, and four died of complications referable to other organs-quite an encouraging record in a few cases. Finally, I may be permitted to summarize these conclusions as follows: 1. Suture of a wound of the heart as a final resort is an operation worthy of consideration in some cases and often justifiable. 2. Suture of wounds of the heart in animals, and also in man, is devoid of the danger of sudden arrest of the heart, due to the manipulation of the heart incident to the procedure, unless Kronecker's coördination centre be injured. 3. The suture should be an interrupted one of silk, applied in most cases so that the epicardium and superficial layers of the myocardium should be the only ones penetrated, and tied, when possible, during diastole. 4. No stated indications can be given as to the cases that are operable or the time when the operation should be done. Each case must be considered by itself for symptoms which would justify operative interference.

19866920

1895-1899

A CASE OF ACUTE ENDOCARDITIS CAUSED BY MICROCOCCUS ZYMOGENES (NOV. SPEC.), WITH A DESCRIPTION OF THE MICROORGANISM.

From a case of acute endocarditis of the aortic and mitral valves with infarctions m the spleen and kidneys a micrococcus was twice isolated in pure culture from the blood during life and was demonstrated after death both microscopically and in pure culture in large numbers in the valvular vegetations, the infarctions and other parts. No other species of microorganism was found. This micrococcus is very small, occurs mainly in pairs, sometimes in short chains, stains by Gram's method, grows in small, pale, grayish-white colonies on gelatine and agar, at first clouds bouillon, which then becomes clear with a whitish sediment, does not produce gas in glucose media, liquefies gelatine slowly and to some extent also blood serum, and is especially characterized by its behavior in milk, which it acidifies, coagulates and subsequently liquefies. It produces a milk-curdling ferment and also a proteolytic ferment, each of which is separable from the bacterial cells. It remains viable for months in old cultures and is tolerably resistant to the action of heat and antiseptics. The micrococcus is pathogenic for mice and rabbits, causing either abscesses or general infections. Typical acute vegetative endocarditis was experimentally produced by intravenous inoculation of the organism in a rabbit and a dog, and the cocci were demonstrated in pure culture in the vegetations and other parts of these animals after death. Although the micrococcus here described has some points of resemblance to the pneumococcus and Streptococcus pyogenes on the one hand and to the pyogenic staphylococci on the other, it is readily distinguished from each of these species by cultural features which have been described and which are so obvious that the differentiation of these species from our micrococcus need not be discussed in detail. We have searched through the records concerning microorganisms described in association with endocarditis and other diseases, as well as those isolated from water, soil and other sources, and have been unable to find a description of a micrococcus identical in all particulars with that here described. Such points as staining by Gram, liquefaction of gelatine, coagulation and peptonization of milk, served singly or in combination to distinguish our micrococcus from other forms which in some respects might resemble it. We feel justified, therefore, in recognizing this organism as a new species and from its fermentative properties propose for it the name "Micrococcus zymogenes." Micrococcus zymogenes must be added to the already considerable list of bacteria which have been found as the specific infective agents in endocarditis. That it was the cause of this affection in our case was conclusively demonstrated by its repeated isolation in pure culture from the blood during life, by its presence in pure culture and large numbers after death in the cardiac vegetations, the infarctions, and other parts of the body, and by the experimental proof of its pathogenic properties, and notably its capacity to produce vegetative endocarditis by intravenous inoculation in animals.

19866921

1895-1899

BACILLUS PYOCYANEUS AND ITS PIGMENTS.

THE PRINCIPAL CONCLUSIONS THAT SEEM TO ME JUSTIFIED ARE AS FOLLOWS: 1. The fluorescent pigment formed by some varieties of B. pyocyaneus is produced under conditions identical with those governing the production of the pigment by other "fluorescent bacteria." 2. The production of pyocyanin is not dependent upon the presence of either phosphate or sulfate in the culture medium. It is formed in non-proteid as well as in proteid media, but is not a necessary accompaniment of the metabolic activities of the organism (e. g. tartrate solution). 3. The power of producing pyocyanin under conditions of artificial cultivation is lost sooner than the fluorescigenic power. 4. There are greater natural and acquired differences in pyocyanigenic power than in fluorescigenic. 5. The fluorescent pigment may be oxidized slowly by the action of light and air as well as by reagents into a yellow pigment, and pyocyanin may be similarly oxidized into a black pigment. 6. A convenient separation of B. pyocyaneus into four varieties would be the following: var. alpha, pyocyanigenic and fluorescigenic (most common); var. beta, pyocyanigenic only (rare); var. gamma, fluorescigenic only (not uncommon, closely related to "B. fluorescens liquefaciens"); var. delta, non-chromogenic. 7. Except for the occasional loss of one or another function the different varieties are not so plastic as sometimes assumed, and cannot be readily converted into one another by subjection to varying conditions of life. 8. The signification and correlation of the almost countless physiological variations among the members of this group in respect to growth in gelatin, behavior to temperature, indol production, etc., remain to be determined. It is not yet clear that the variations in chromogenic power can be in any way correlated with the presence or absence of other physiological functions.

19866929

1895-1899

AN EXPERIMENTAL STUDY OF OXALURIA, WITH SPECIAL REFERENCE TO ITS FERMENTATIVE ORIGIN.

1. As varying amounts of calcium oxalate may be held in solution in the urine, conclusions based upon the presence or number of calcium oxalate crystals found therein are of no real value as an indication of the quantity of oxalic acid present. 2. Unless the utmost care is exercised, the results obtained by quantitative estimation of oxalic acid are subject to large percentages of error. This is especially true in the use of Neubauer's or Shultzen's methods, in which the calcium oxalate is precipitated in an alkaline solution. 3. An ordinary mixed diet regularly contains traces of oxalic acid or its salts. 4. A portion of the oxalic acid ingested with the food may be absorbed and reappear unchanged in the urine. 5. The normal daily excretion of oxalic acid in the urine fluctuates with the amount taken in the food, and varies from a few milligrammes to two or three centigrammes, being usually below ten milligrammes. 6. In health, no oxalic acid, or only a trace, is formed in the body, but that present in the urine has been ingested with the food. 7. In certain clinical disturbances which in some of the cases studied above were associated with absence of free hydrochloric acid from the gastric juice, oxalic acid is formed in the organism. 8. This formation in the organism is connected with fermentative activity in the alimentary canal. (a) The prolonged feeding of dogs with excessive quantities of glucose, together with meat, leads eventually to a state of oxaluria. (6) This experimental oxaluria is associated with a mucous gastritis, and with absence of free hydrochloric acid in the gastric contents. (c) The oxaluria and the accompanying gastritis are referable to fermentation induced by the excessive feeding with sugar. (d) The experimental gastritis from fermentation is associated with the formation of oxalic acid in the gastric contents. 9. The symptoms attributed to an oxalic acid diathesis, with the exception of those due to local irritation in the genitourinary tract, do not appear to be due to the presence in the system of soluble oxalates, but are more likely to depend on other products of fermentation and putrefaction.

19866934

1900-1904

SERUM-GLOBULIN AND DIPHTHERIC ANTITOXIN.-A COMPARATIVE STUDY OF THE AMOUNT OE GLOBULIN IN NORMAL AND ANTITOXIC SERA, AND THE RELATION OF THE GLOBULINS TO THE ANTITOXIC BODIES.

THE RESULTS OF THE FOREGOING EXPERIMENTS MAY BE BRIEFLY SUMMARIZED AS FOLLOWS: The amount of antitoxic substance obtained by precipitation with magnesium sulphate from the blood-serum of the horse corresponds, as nearly as can be determined by the use of test guinea-pigs, in full to the protective power of the serum from which it is obtained, i. e. the precipitate from 1 cc. of serum will protect against the same amount of toxin as 1 cc. of the serum itself. Equal amounts of the precipitates by magnesium sulphate from immunized and non-immunized horses act differently toward toxin; i. e. the proportion of protective substance to the precipitate from non-immunized serum is exceedingly small as compared with the proportion of antitoxin to the precipitate from sera of immunized horses. The average precipitate from the sera of immunized horses, as obtained by magnesium sulphate, is more abundant than the average precipitate from sera of non-immunized horses. In the case of the same animal before and after immunization, the serum before immunization gives a less abundant precipitate with magnesium sulphate than the serum tested after immunization. The proportion of increase per unit of antitoxic strength for the same or different horses is not constant. This may be due to an increase of inactive substances (in their relation to diphtheric toxin) or to imperfect methods of determination. The precipitates obtained by magnesium sulphate give all the reactions recognized as characteristic of globulins, and as distinguishing them from other albuminous bodies. We are not warranted, then, in the present state of our knowledge, in considering any part of these precipitates as other than globulin. But it does seem warrantable to conclude, from the fact that the globulins of normal serum do not protect, or only in comparatively large amounts, against diphtheric toxin, that new globulins are formed, or rather greatly increased in the serum of immunized horses, and that these globulins protect against the toxin. These increased globulins and the inert globulins (which from obvious causes are a very variable factor) are both precipitated by magnesium sulphate. Every animal has a physiological and pathological history more or less widely diverging from the normal, hence absolute conformity in the results obtained is not to be expected, at least with our present methods of differentiation.

19866935

1900-1904

THE FRACTIONAL PRECIPITATION OF THE GLOBULIN AND ALBUMIN OF NORMAL HORSE'S SERUM AND DIPHTHERIA ANTITOXIC SERUM, AND THE ANTITOXIC STRENGTH OF THE PRECIPITATES.

1. The globulins of both normal and diphtheria antitoxic serum exhibit chemically toward reagents the same reactions, being precipitated by magnesium sulphate and split up into fractions in precisely the same way. 2. All of the diphtheric antitoxic power of both normal and immunized serum is always carried by the globulin and its fractional precipitates. 3. During the fractional precipitation of the serum globulin of horses immunized from diphtheria toxin and horses not immunized from diphtheria toxin, some of the globulin is lost, likewise at the same time some of the antitoxic power of the globulin of the immunized serum is lost. 4. These reactions, considered in connection with the fact that different observers as well as we ourselves have found diphtheric antitoxic power in normal horse's serum and that this antitoxin separates with the globulin, strongly incline us to consider "diphtheria antitoxin" a form of globulin. 5. The reactions of globulin, previously separated from the serum by magnesium sulphate, with sodium chloride lead one to think that there is a formation of globulin salts. 6. Since serum albumin in a magnesium sulphate solution gives fractional precipitates at definite temperatures, it seems not improbable that the albumin is precipitated in the form of albumin salts.

19866936

1900-1904

A CASE OF GENERAL GASEOUS EMPHYSEMA WITH GAS CYSTS IN THE BRAIN FORMED AFTER DEATH AND DUE TO BACILLUS MUCOSUS CAPSULATUS, WITH A CONSIDERATION OF THE GAS-PRODUCING PROPERTIES OF CERTAIN MEMBERS OF THIS GROUP IN THE CADAVERS OF ANIMALS.

In the case reported in this article there was septicaemia with special localization of the microorganisms in the brain, with gas cysts of the brain and general gaseous emphysema due to Bacillus mucosus capsulatus (aërogenes group). The bacillus isolated from the organs of this case, as well as other members of the aërogenic group of Bacillus mucosus capsulatus can cause general gaseous emphysema in the cadavers of rabbits, either with or without the intravenous injection of sugar before the animal is killed, the gas, however, being most abundant and rapidly formed in the former case. It is not impossible that some of the published cases of gaseous emphysema in which a bacteriological examination was not made, may have been due to members of the Bacillus mucosus capsulatus group.

19866941

1900-1904

A PRELIMINARY REPORT ON ACID-RESISTING BACILLI, WITH SPECIAL REFERENCE TO THEIR OCCURRENCE IN THE LOWER ANIMALS.

THE RESULTS OBTAINED IN THIS STUDY MAY BE BRIEFLY SUMMARIZED: 1. Acid-resisting bacilli are found in many of the lower animals, more especially the horse, cow, dog, guinea-pig and white rat. In the case of the rabbit and cat no such organisms were detected. 2. Many of these acid-resisting bacilli resemble the tubercle bacillus and the smegma bacillus of man. 3. The acid-resisting organisms are undoubtedly of different species and there is good reason to believe that the term smegma bacillus denotes not a definite species but rather a group of bacilli having common staining properties.

19866944

1900-1904

A COMPARATIVE STUDY OF THE BIOLOGICAL CHARACTERS AND PATHOGENESIS OF BACILLUS X (STERNBERG), BACILLUS ICTEROIDES (SANARELLI), AND THE HOG-CHOLERA BACILLUS (SALMON AND SMITH).

1. Bacillus X (Sternberg) belongs to the colon group. 2. Bacillus icteroides (Sanarelli) is a member of the hog-cholera group. 3. The various channels of infection, the duration of the disease and the gross and microscopical lesions in mice, guinea-pigs and rabbits are the same for Bacillus icteroides and the hog-cholera bacillus. 4. The clinical symptoms and the lesions observed in dogs inoculated intravenously with Bacillus icteroides, are reproduced in these animals by infection with the hog-cholera bacillus. 5. Bacillus icteroides when fed to the domestic pig causes fatal infection, accompanied by diphtheritic, necrotic and ulcerative lesions in the digestive tract, such as are seen in hogs when infected with the hog-cholera bacillus. 6. This disease may be acquired by exposing swine in pens already infected with Bacillus icteroides, or by feeding them with the viscera of infected pigs. 7. Guinea-pigs may be immunized with sterilized cultures ofBacillus icteroides from a fatal dose of the hog-cholera bacillus and vice versa. 8. Rabbits may be rendered immune by gradually increasing doses of a living culture of Bacillus icteroides of weak virulence from a fatal dose of a virulent culture of the hog-cholera bacillus 9. The sera of animals immunized with Bacillus icteroides and with the hog-cholera bacillus, respectively, show a marked reciprocal agglutinative reaction. 10. While the blood of yellow fever practically does not exercise an agglutinative reaction upon Bacillus icteroides, the blood of hog-cholera agglutinates this bacillus in a much more marked degree, thus pointing, we think, to the closer etiological relationship of this bacillus to hog-cholera than to yellow fever.

19866945

1900-1904

THE RELATIONS OF THE NORTH AMERICAN FLORA TO THAT OF SOUTH AMERICA.

Reviewing the floral relations of North and South America as illustrated in the foregoing instances, we may say that the phenomena of distribution agree fairly with the record of physical conditions which have succeeded each other and those which still exist, and upon which we might almost a priori have predicted an analogous set of distribution phenomena. In this relationship we may distinguish three categories of distribution: (1) Those due to the conditions of human civilization, commerce, etc. This has resulted in placing the same species in similar regions of both continents, as, for example, Fagonia cretica in Lower California and Chile; Munroa squarrosa, western plains of North America, plains of Argentine and high plateaus of Chile and Bolivia; Frankenia grandiflora, Southern California and Arizona, coast lands of Chile; Oxytheca dendroidea, Lastarricea chilensis, and Chorizanthe comrnmissuralis, all in Southern California and Western Chile. (2) Those due to the operation of natural causes acting unde present conditions of climate, geology, etc. Under this head may be cited such species as sida leprosa, hastata, anomala, Cienfugosia sulphurea, Spergulariaplattensis and, in general, elements of Gulf zone distribution; also certain elements which still find a pathway along the continental axis, including some alpine and mountain xerophilous genera. (3) The third category of distribution would include those phenomena due to geological and climatic changes acting through long periods. Under this head are included the elements of greatest significance in the relationsip of the North and South America floras. The endemic boreal flora of the Andes, the equally endemic boreal flora of the Mexican Cordilleras, and genera with sharply distinct species or sub-genera in the arid extra-tropical regions of both continents, which may be called remnant elements.

17832120

1900-1904

ON THE RELATION OF CHRONIC INTERSTITIAL PANCREATITIS TO THE ISLANDS OF LANGERHANS AND TO DIABETES MELUTUS.

Congenital syphilitic pancreatitis retards the development of the glandular acini but does not affect the islands of Langerhans. Embedded in the stroma, but not invaded by it, the latter maintain their continuity with the small ducts and acini with which they have a common origin. (2) Two types of chronic interstitial inflammation affecting the developed pancreas are distinguishable: (a) Interlobular Pancreatitis.-In the interlobular variety the inflammatory process is localized chiefly at the periphery of the lobule and implicates the islands of Langerhans only when the sclerotic process has reached a very advanced grade. When pancreatitis has followed obstruction of the ducts, the islands long remain unaltered though embedded in dense scar-like tissue. (b) Interacinar Pancreatitis.-In the interacinar type the process is diffuse, invading the lobules and separating individual acini. The inflammatory change invades the islands of Langerhans. (3) A relationship has been observed between lesions of the islands of Langerhans and the occurrence of diabetes mellitus. (a) In one of eleven cases of interlobular panereatitis diabetes of mild intensity occurred. The sclerosis, which in this case followed obstruction of the ducts by calculi, was far advanced and affected the islands of Langerhans. (b) In two of three cases of interacinar pancreatitis, diabetes was present. The third case was associated with a condition, haemochromatosis, which at a later stage is associated with diabetes, the result of pancreatic lesion. (c) In a fourth case of diabetes, hyaline deposit between the capillaries and the parenchymatous cells had so completely altered the islands of Langerhans that they were no longer recognizable.

19866952

1900-1904

THE NERVES OF THE CAPILLARIES, WITH REMARKS ON NERVE-ENDINGS IN MUSCLE: A NEW THEORY OF LYMPH-FORMATION AND OF GLANDULAR SECRETION.

1. The endings of the motor nerves in striped muscle remain on the outside of the sarcolemma. Aside from the surfaces of contact of muscle and nerve fibre, the end fibres are covered down to their tips with the sheath of Schwann and are provided with nuclei. The precise condition of things at the places of contact of muscle and nerve is an unsolved problem of histology. 2. The ivy-like or festooned arrangement of motor nerves in the frog's muscle has been misinterpreted. Properly interpreted it demonstrates that the nerve fibres that are to influence the muscle fibre are not naked and that they need not be end fibres. It shows that mere contact between muscle fibre and nerve fibre is all that is necessary. 3. The sheath of Henle in the frog and in the smaller muscle fibres of the snake is open, thus permitting escape of the cerebrospinal fluid. 4. In other animals Henle's sheath extends over the end fibres of the motor nerve and the cells lining it envelop the end fibrils. I find that the so-called "Sohlensubstanz" of Kühne is derived from the cells of Henle's sheath. 5. The terminal nerves in smooth muscle form a network entwining the bundles of muscle fibres. I consider it improbable that each plain muscle fibre has a special terminal nerve fibril. 6. In muscular tissue fine non-medullated nerves, probably belonging to the centrifugal, vasomotor system, proceed from the fasciculi of motor nerves. These nerves can be traced directly to a network of nerves surrounding the capillaries. From this network fine, nucleated, nerve fibres pass to the walls of the capillaries, with which they are very closely united. 7. The nerves supplying the capillaries connect also with sensory nerves and with nerves surrounding the larger blood-vessels, both arteries and veins. 8. The branches of the chorda tympani in the submaxillary gland do not pass to the gland cells, but they terminate on the capillaries. 9. In muscular and glandular tissues-and perhaps throughout the body-there is a vast peripheral nervous plexus belonging to the capillary blood-vessels. These nerves of the capillaries, which may perhaps be regarded as nutritive nerves, regulate the production and transudation of lymph, and are concerned in the mechanism of glandular secretion. They may be called into activity both by peripheral influences and by impulses received from the central nervous system and the sympathetic ganglia. They may influence, through their connections with the vasomotor nerves on the arteries and veins, the blood supply to a part.

19866954

1900-1904

THE INFLUENCE OF BILE ON METABOLISM.

1. Bile increases the digestion of fat when given by the mouth in pill form. The percentage of fat lost in the stools of our patient with a complete biliary fistula was 63 per cent in the first period and 57 per cent in the third. This closely corresponds to the results that Müller obtained in human beings and dogs with complete obstruction of the common duct. Under bile medication the stools contained 23 per cent less fat than in the first period, and 17 per cent less than in the third. This represents an actual diminution of the amount of fat lost in the stools. Looking at the result in another way, it may be said that the average digestion of fat in the periods without bile was 40 per cent; in the periods with bile, 60 per cent, i. e., bile increased the digestion of fat relatively by 50 per cent. 2. The digestion of nitrogenous food is improved by the use of bile pills when the amount of fat in the stools is large. Instead of an average of 15 per cent being lost in the faeces, but 7 per cent escaped digestion during the four days the patient took bile. The reason for this, perhaps, lies in the better digestion of fat at this time, in consequence of which the proteid elements of the food were more thoroughly exposed to the digestive juices. 3. Ox bile is a cholagogue. The amount of bile-solids secreted in the bile period was 47 per cent greater than in the periods before and after. This confirms the work of Pfaff and Balch, here in Boston, on a human being, and that of Stadelmann and his pupils, in Germany, on dogs. 4. The effect of the bile on the bowels in this case was not remarkable, although they moved more satisfactorily during the bile period. In my experiments with dogs I usually obtained diarrhoea when giving bile. I do not feel sure, however, that this should be attributed wholly to the medication, for the diarrhoeas as a rule appeared six or more days after the beginning of the experiment and the animals were then in poor condition. Dr. Pfaff, who has had more experience with the administration of bile than I, tells me that he has found its action variable in patients. In some cases it is a laxative; in others, in which there is diarrhoea, due apparently to large amounts of fat in the food, it has the opposite effect. 5. As to the general effect of bile on body metabolism, it was observed that the urea and nitrogen were excreted in greater amount in the bile period than in either of the others. No definite conclusions can be drawn from this fact, because more nitrogen was ingested during these four days; moreover, it must be borne in mind that in these results the salol may have been a factor. 6. The amount of urine was increased by more than 50 per cent in the bile period. It is interesting to note that the amount was about the same during this bile period as in the second experiment when the bile was again taking its natural course. Von Noorden has recorded a similar increase in the amount of urine following the removal of the obstruction in acute catarrhal jaundice. The salol coating of the bile pills, which amounted to one and a quarter grammes a day, is not sufficient to account for this effect. This is evident from the work of Kumagawa, who gave two grammes of sodium salicylate daily to a dog of 25 kilos without essentially changing the amount of urine secreted. On the other hand, in taking the 30 pills daily the patient drank several extra glasses of water, and in the second experiment her general condition was naturally better than at any other time.

19866955

1900-1904

ALLOXURIC EXCRETION IN A CASE OF LEUCOPENIA.

1. In the case investigated, one of Malta fever, the leucocytes were reduced to between 1500 and 3000 per cubic millimetre. 2. Notwithstanding this, the alloxur bodies and the phosphoric acid in the urine, the patient being on an alloxur-free diet, showed no distinct diminution from the normal. 3. The suggestion is made that this result may be due to the leucopenia being brought about by an increased destruction of leucocytes in the spleen rather than to a diminished activity of the bone-marrow.

19866957

1900-1904

THE ACID INTOXICATION OF DIABETES IN ITS RELATION TO PROGNOSIS.

IT SEEMS DESIRABLE TO EMPHASIZE THE FOLLOWING CONCLUSIONS: 1. A careful balancing of the normal acids and bases of the urine makes it possible not merely to detect the presence of organic acids in the urine, but also to determine approximately the amount of such acids. The method recently described by Herter and Wakeman can be recommended as securing a greater degree of accuracy, for the amount of labor involved, than any other procedure. 2. The determination of the N of NH(3) is a useful procedure for clinical purposes, since it is probably true that a considerable excretion of organic acid (say 15 gm. oxybutyric or more in 24 hours) is always attended by an increased excretion of NH(3). As much organic acid as corresponds to 10 gm. oxybutyric acid may be excreted in 24 hours without causing an increased excretion of NH(3) (Case IX). We cannot therefore rely on the ammonia output to detect moderate quantities of organic acid. 3. Where organic acids are removed in considerable amount without increasing the excretion of NH(3), the acid takes out other alkalies, probably in some instances chiefly K. 4. In cases of diabetic coma the urine always contains a large excess of organic acids and the N of NH(3) is usually increased to 18 to 25 per cent of the total N. 5. Crotonic acid can regularly be obtained from the urines of patients in diabetic coma. 6. The condition of diabetic coma is preceded by a period of days, weeks or months, in which there is a large excretion of beta-oxybutyric acid (20 gm. or more in 24 hours), and in which the N of NH(3) is largely increased. 7. Patients whose urines show or have shown a large excretion of organic acids are in danger of developing diabetic coma, but the N of NH(3) may temporarily rise as high as 16 per cent and yet coma may be delayed for more than 7 months (Case VII). The persistent excretion of more than 25 gm. of beta-oxybutyric acid indicates impending coma. 8. A patient passing 30 gm. of beta-oxybutyric acid in 24 hours may still have enough energy and strength to be about all day and perform considerable muscular work (Case X). 9. A patient who has been excreting very little organic acid and has gained weight may within a few months show the presence of considerable quantities of organic acid, and die in typical diabetic coma (Case VII). 10. When the urine contains little or no organic acid there is no immediate prospect of diabetic coma, but patients with such urine are probably liable to most of the other dangers that threaten diabetic patients. The relation between the degree of acid intoxication and the susceptibility to infection seems worthy of special experimental study. 11. Where the urine regularly contains more than 200 gm. of sugar per day there is usually considerable organic acid in the urine and large amounts of acid, indicative of coma, are invariably accompanied by considerable or great glycosuria. 12. Sometimes there is much sugar and little or no acid in the urine, and sometimes there is considerable acid and little sugar. These facts render it desirable to examine the urine of diabetic patients at least once a month with reference to the amount of acid excreted, for the element of acid intoxication must be clearly separated from the element of glycosuria in our study of the progress of a case. In other words, we must recognize the acid intoxication as an important and sometimes as a dominant factor in the prognosis, and this element should be regarded even in those cases of diabetes which have the clinical indications of a mild type of the disease. We may thus hope to prolong life in many instances by taking precautions, as to diet and out-of-door life, which might not otherwise be deemed necessary. 13. The withdrawal of carbohydrate food frequently leads to a considerable reduction in the quantity of organic acids excreted. The reason for this is not yet clear and the phenomenon deserves careful study.

19866959

1900-1904

NOTES UPON THE AGGLUTINATIONS OBTAINED BY INTRAPERITONEAL INSERTION OF CELLOIDIN CAPSULES CONTAINING BACILLI AND UPON A MODE OF PREPARING SUCH CAPSULES.

1. Capsules made as described above allow dialysis, when placed in the peritoneal cavity. 2. The normal tissues, unstimulated, do not possess the power of causing agglutination; they do not require to be stimulated by the presence of the bacterial bodies, but will produce their share of the agglutinins when acted upon by the bacillary products. 3. Agglutination follows the insertion, in the peritoneal cavity, of "capsuled" bacilli; it gradually increases in degree, and on the removal of the capsule containing the bacilli, begins to disappear. 4. Varieties of bacilli, related closely in morphology and cultural reactions, do not, as a rule, produce serums which inter-agglutinate.

19866960

1900-1904

OBSERVATIONS ON A CASE OF CYCLIC ALBUMINURIA.

The preceding observations record a new instance of the occurrence of cyclic albuminuria in an otherwise apparently healthy young man. The typical course of the proteid excretion from hour to hour under various conditions has been reviewed and its independence of the changes in diet or muscular work pointed out. No relationship between the volume of urine eliminated and the quantity of proteid excreted has been ascertained. The specific effect of the horizontal posture in dispelling the albuminuria is the most interesting feature observed. The attempt to refer this to attendant circulatory changes in the kidneys is, for the present, no more than an interesting speculation. See PDF for Structure See PDF for Structure.

19866962

1900-1904

THE ETIOLOGY OF ACUTE DYSENTERY IN THE UNITED STATES.

1. The several standard cultures used in this study are indistinguishable -a conclusion previously reached and stated by Flexner. 2. The acute dysentery of the United States is due to a bacillus indistinguishable from that obtained from the epidemics of dysentery in several other parts of the world. 3. The sporadic and the institutional outbreaks of acute dysentery are caused by the same microorganism, and this organism is identical with that causing epidemic acute dysentery. 4. The cause of acute dysentery, whether sporadic, institutional, or epidemic, is Bacillus dysenteriae Shiga.

19866970

1900-1904

EXPERIMENTS ON THE EFFECTS OF INJECTION OF EGG-ALBUMEN AND SOME OTHER PROTEIDS.

THE CONCLUSIONS WHICH WE DERIVE FROM OUR OBSERVATIONS ARE AS FOLLOWS: 1. The excretion of injected, egg-albumen as such is in no case complete. The quantity retained varies from 23 to 100%. 2. The amount retained varies: a) directly with the slowness of absorption. This is determined by the manner of administration. b) directly with the time during which the proteid remains in the body; and therefore inversely to the rapidity of excretion. c) inversely to the quantity injected; this has however much less effect than (a) or (b). d) with individual peculiarities; but these are not very conspicuous. 3. The excreted proteid coagulates at the same temperatures as the injected albumen. 4. Injection of egg-albumen does not cause the appearance of globulins in the urine. 5. The proportion of proteid coagulating at lower temperatures is less in the urine than in the injected solution. When a solution has been heated to 73 degrees before injection, the urine also does not coagulate below this temperature. 6. Egg-albumen injected into the hen is excreted as with mammals. 7. The albuminuria lasts in typical cases from 1(1/2) to 3 days, according to the manner of administration. The excretion begins very shortly (7 minutes) after injection. 37 per cent of the total proteid injected may be excreted in an hour. About three-fourths of the total excretion takes place within the first 17 hours; the excretion is almost completed in the next 15 hours, only traces being excreted thereafter. With hypodermic injection the amount is more nearly equal on 2 or 3 successive days, since the absorption may extend over 2 days. 8. Alkali-albumin, as well as muscle-proteids (from foreign species) are completely retained. An unconverted mixture of egg-albumen and sodium carbonate behaves like egg-albumen. 9. A small amount of proteid (less than 5%) is excreted unchanged by the faeces. 10. A variable proportion is excreted as non-coagulable proteid. The quantity of this is proportional to that of the coagulable proteid of the urine. 11. The rest undergoes complete metabolism to urea. 12. The total nitrogen excretion is increased beyond the amount of nitrogen introduced as albumen. 13. Starvation appears to cause an increase in the ratio of the urea to the total nitrogen of the urine. 14. The effects of intravenous injection of egg-albumen on circulation and respiration do not differ from those of an equivalent injection of the solvent. Albumen causes, however, a specific diuresis, beginning 50 minutes after the intravenous injection, and reaching its maximum in about 2 hours. It causes neither glycosuria nor haemoglobinuria. 15. The injection of egg-albumen, alkaline egg-syntonin, or muscle extracts, causes in rabbits a rise of temperature of 1 to 2 degrees C. This begins in about an hour, usually reaches its maximum in from 6 to 8 hours, and then falls rapidly. It may in rare cases persist for several days. It is indifferent qualitatively whether the injection is made by the jugular or the ear-vein, hypodermically, or into the peritoneum. Even extremely small quantities injected into the ear-vein cause this rise. The fever does not cause histological alterations in any organ examined. The injection of normal salt solution may cause a rise, but this is much smaller. 16. The injection of egg-albumen causes but very slight histological changes. The kidneys are usually congested, especially in the cortex. The cells may be slightly cloudy. A slight degree of nephritis may occur, but this is not of such degree as to effect permanent lesions. The injection of muscle extracts may give rise to a more pronounced parenchymatous nephritis. 17. Urethane is fatal to rabbits in doses of 0.75 to 1.0 grm. per kilo. The symptoms consist mainly in a very marked fall of temperature, and in medullary paralysis. 0.5 grm. per kilo. lowers the temperature 2.3 degrees C. Doses as small as 0.6 grm. per kilo cause very marked histological changes, consisting mainly in extensive granular and vacuolar degeneration of the hepatic epithelium, which are so acute as to be fully developed when death occurs in 1(1/2) hours after injection. Doses of 0.35 grm. per kilo. do not produce this change. Chloretone did not cause the degeneration, but is followed by congestion of the abdominal viscera. 18. Native egg-albumen, injected into the femoral vein of a dog, was followed in one case by a fatal ending with convulsions and coma, after several intervening cases of good health. Further experiments demonstrated that there is no toxicity inherent in fresh egg-albumen, nor can it be developed by breeding the eggs in the shell. The cause of the above fatal issue must therefore be sought in some extraneous toxic agent which contaminated the solution. Muscle-extracts were also devoid of toxicity. Alkali-albumin produces no changes beyond those which may be attributed to the free alkali contained therein.

19866971

1900-1904

A CONTRIBUTION TO OUR KNOWLEDGE OF THE ACTION OF SAPONIN ON THE BLOOD CORPUSCLES AND PUS CORPUSCLES.

1. The increase of conductivity produced by saponin in formaldehyde-hardened blood is due to an increase in the conductivity of the corpuscles (increased permeability of the corpuscles to ions) and not, mainly at any rate, to the liberation of electrolytes from the corpuscles and a consequent increase in the conductivity of the serum. The increase in the permeability of the corpuscles is probably caused by a "corrosive," dissolving, or emulsifying action of the saponin on some non-proteid constituent of the envelope or stroma. 2. In the first stage of the action of saponin on blood (not fixed by formaldehyde) there seems also to be an increase in the permeability of the corpuscles for ions, even before any haemoglobin has been liberated. The liberation of the haemoglobin may be secondary to this, owing to the entrance, of water consequent on the disturbance of osmotic equilibrium. 3. Heating the blood to 40 degrees to 45 degrees C. intensifies the laking action of saponin, so that a dose insufficient to cause laking at ordinary temperature may do so when the blood is heated to the temperature mentioned. 4. Pus corpuscles, like red blood corpuscles, are worse conductors than the serum in which they are suspended. Unlike blood corpuscles, they show no preference for NH(4)Cl as compared with NaCl. On the other hand, the conductivity of pus is increased by the action of saponin, just as is the case with blood, and apparently very much in the same way, that is to say, by an action on the corpuscles and not on the serum. The fixing of the pus corpuscles by formaldehyde does not hinder this action of saponin.

19866972

1900-1904

The surgical treatment of sterility due to obstruction at the epididymis; together with a study of the morphology of human spermatozoa.

In a report of 192 cases of examinations of both husband and wife for cause of sterility, the husband was found at fault in 33 cases. In 31, few spermatozoa were present and in 2, none. The morphology of human spermatozoa is described in detail and the results of various staining methods compared. Numerous drawings illustrate observed variations in morphology. The common cause of azoospermia is an obliterating double epididymitis, usually of gonorrheal origin. Permanent obliteration of the tube of the epididymis is exceptional rather than usual. Persistent obstruction is most often only in the tail of the epididymis. Motile spermatozoa may be found above the block. The obstructed area may be bypassed by attaching the vas to any part of the epididymis on the testicular side of the obstruction or to the vasa efferentia. This operation was successfully accomplished first in experiments on dogs. A trial operation was done on a man with a history of bilateral epididymitis of gonorrheal origin followed by aspermia. The cut end of the vas deferens was implanted into an incision in the head of the epididymis and secured with silver-wire sutures. Semen showed many spermatozoa 19 days postoperation. Whether the continuity of the duct will be permanently maintained was not determined.

12255534

1900-1904

MENDEL'S LAW OF HEREDITY.

1. The basic principle in Mendel's discoveries is that of the purity of t. he germcells; in accordance with this a cross-bred animal or plant produces germ-cells bearing only one of each pair of characters in which its parents differ. From it follows the occurrence in the second and later hybrid generations of a definite number of forms in definite numerical proportions. 2. Mendel's principle of dominance is realized in the heredity of a considerable number of characters among both animals and plants. In accordance with this principle, hybrid offspring have visibly the character of only one parent or the other, though they transmit those of both parents. 3. In other cases the hybrid has a distinctive character of its own. This may approximate more or less closely the character of one parent or the other, or it may be entirely different from both. Frequently the distinctive hybrid character resembles a lost ancestral character. In some cases of this sort, as in coat-color of mammals, the hybrid character probably results from a recomibination of the characters seen in one or both parents, with certain Other characters latent (that is, recessive) in one parent or the other. 4. There have been observed the following exceptions to the principle of dominance, or to the principle of purity of the germ-cells, or to both: (a) Mosaic inheritance, in which a pair of characters ordinarily related as dominant and recessive occur in a balanced relationship, side by side in the hybrid individual and frequently in its germ-cells also. This balanced condition, once obtained, is usually stable under close breeding, but is readily disturbed by cross-breeding, giving place then to the normal dominance. (b) Stable (self-perpetuating) hybrid forms result from certain crosses. These constitute an exception to both the law of dominance and to that of purity of the germ-cells. For the hybrid is like neither parent, but the characters of both parents exist in a stable union in the mature germcells produced by the hybrid. (c) Coupling, i. e., complete correlation may exist between two or more characters, so that they form a compound unit not separable in heredity, at least in certain crosses. (d) Disintegration of characters apparently simple may take place in consequence of cross-breeding. (e) Departures from the expected ratios of dominants to recessives may be explained in some cases as due to inferior vigor, and so greater mortality, on the part of dominants or recessives respectively. (f) Cases of apparent reversal of dominance may arise from 'false hybridization' (induced lparthenogenesis). Possibly in other cases the determination of dominance rests with circumstances as yet unknown. 5. Mendel's principles strengthen the view that species arise by discontinuous variation. They explain why new types are especially variable, how one variation causes others, and why certain variations are so persistent in their Occurrence.

17752783

1900-1904

Ovarian transplantation and reconstruction of fallopian tubes: with report of two cases and review of literature.

2 very early cases of organ transplantation, in this case of sections of healthy ovaries from fertile women to women unintentionally or unknowingly subjected to oophorectomy, are described; the paper concentrates on surgical technique, for the outcome is preliminary at the time of publication. The surgeon involved found donors willing to lose portions of their ovarian tissue, for various reasons, who were proven fertile. In 1 case of transplantation, the recipient was made ready for transplantation concurrently with the donor, and no storage of organs was necessary; in the other, ovarian material was stored in saline for a period of time, and upon reintroduction to a pelvic cavity the material immediately became reinfused and appeared healthy. Neither of the recipients had begun menstruating postsurgery at the time of this article's publication (about 6 months postoperatively), but signs were hopeful. The technique is spelled out in a step-wise manner.

12336567

1900-1904

A CONTRIBUTION TO THE PHYSIOLOGICAL DIFFERENTIATION OF PNEUMOCOCCUS AND STREPTOCOCCUS, AND TO METHODS OF STAINING CAPSULES.

By morphological examination and with current cultural methods a clear differentiation cannot always be made between pneumococci and streptococci. The chief differential character usually depended upon is the capsule of the pneumococcus. Well-marked capsules, however, may occur on organisms which have with reason been classified as streptococci. On the other hand, capsules may not he demonstrable on pneumococci by the usual methods, especially when growing on artificial culture media. The usual cultural characters and reactions are at best not diagnostic, and are subject to variations which may render them useless as evidence of specific difference. The experiments recorded in this paper, however, afford some evidence that there are well-marked differences between the metabolic activities of pneumococci and streptococci, which may prove useful in the differentiation of these organisms. These differences in metabolism become apparent when the pneumococci and streptococci are cultivated in an alkaline serum medium, or in a serum medium to which the carbohydrate, inulin, has been added. Pneumococci slowly produce acid in the alkaline serum.

19866975

1905-1909

FURTHER OBSERVATIONS ON A PATHOGENIC MOULD FORMERLY DESCRIBED AS A PROTOZOON (COCCIDIOIDES IMMITIS, COCCIDIOIDES PYOGENES).

FROM THE PRECEDING I DERIVE THE FOLLOWING CONCLUSIONS: 1. The disease which formerly has been described as a form of protozoon-infection is due to an infection with a pathogenic fungus. 2. The infection may primarily be either a cutaneous or a pulmonary one. 3. The lesions produced by this fungus fall under the general head of infectious granulomata and consist partly in nodules resembling altogether those produced by the tubercle bacilli and partly in chronic abscesses. 4. The adult forms of the parasite are more apt to produce nodules, the sporulating forms abscesses. 5. The fungus is pathogenic for dogs, rabbits and guinea-pigs probably other animals also, and in them produces lesions very similar to those which we encounter in the human being in this disease. 6. Supurative periorchitis in guinea-pigs is not pathognomonic for glanders.

19866981

1905-1909

THE TOXIC EFFECTS OF FORMALDEHYDE AND FORMALIN.

THE RESULTS OF THIS INVESTIGATION MAY BE SUMMARIZED AS FOLLOWS: 1. The inhalation of formaldehyde gas in even small quantities is followed by bronchitis and pneumonia. Pneumonia is due to the inhalation of the gas and not to secondary infection. 2. Formalin belongs to that rare group of poisons which are capable of producing death suddenly when swallowed. 3. The introduction of formalin into the stomach is followed by the production of a gastritis which varies greatly in character. The duodenum and upper jejunum may also be involved in the inflammatory process. 4. Intraperitoneal injections of formalin cause peritonitis of a fibrino-haemorrhagic character. A definite reaction is obtained when very dilute formalin is employed. In the peritoneal cavity formalin exercises a destructive action upon all organs (pancreas, liver, peritoneal fat, Fallopian tubes, etc.) with which it comes in contact and causes inflammation in these organs. 5. The lethal dose of formalin when injected intraperitoneally into guinea pigs is approximately 2 cc. of 1-1000 formalin for each 100 grm. of body weight. 6. The injection of formalin into the lungs is followed by pneumonia and bronchitis. 7. The inflammation which follows subcutaneous injections of formalin is characterized by intense exudation. 8. The injection of formalin into the muscles produces myositis. 9. The injection of formalin into the anterior chamber of the eye causes the accumulation of an exudate containing leucocytes and fibrin. When formalin is dropped into the conjunctival sac iritis follows and may be severe enough to destroy the eye. 10. Formalin in whatever way introduced into the body is absorbed, and is then capable of producing lesions in the parenchymatous organs. 11. Changes in the liver after absorption of formalin consist of mild or severe grade of cloudy swelling accompanied by vacuolation of the protoplasm, changes in the nuclei and leucocytic infiltration. Focal necrosis may result. Similar changes follow the inhalation of formaldehyde. 12. The injection of formalin or the inhalation of the vapors of formaldehyde produces cloudy swelling of the parenchyma of the kidney. Focal necrosis may result. 13. Pneumonia and bronchitis are found in all animals after the injection of formalin. 14. The leucocytic infiltration which follows the introduction of formalin into an organ has these general characteristics: The eosinophiles are the first leucocytes to appear; these are followed by the other polynuclear leucocytes; last appear the large and small mononuclear leucocytes. Similar phenomena occur in the trachea, bronchi and lungs of animals subjected to formaldehyde inhalations. 15. Formalin is, directly or indirectly, chemiotactic for leucocytes. The tissues which are not infiltrated with leucocytes after the injection of formalin are those which have been so injured by the chemical that an inflammatory reaction is impossible. 16. Animals subjected to chronic poisoning with formalin administered by intraperitoneal injection develop fibrinous peritonitis, associated with marked eosinophilia. The changes in the kidneys and liver consist of cloudy swelling, fatty degeneration, focal necrosis and leucocytic infiltration.

19866982

1905-1909

"RED-LEG"-AN INFECTIOUS DISEASE OF FROGS.

The epidemics we have observed, were due to the presence and growth in the frogs of Bacillus hydrophilus fuscus. This was proved by recovering the bacillus in pure culture from the body fluids of frogs sick or dead of the disease, and the inoculation of healthy frogs with an emulsion of the pure culture, and by obtaining the same clinical picture and pathological findings as in the original diseased frogs; and, finally, by recovering the bacillus in pure culture from frogs inoculated and sick or dying as a result of the inoculation. The disease is widely distributed throughout North America and Europe, and in this country and Canada is known as "red-leg." It has been observed by us chiefly in the warm weather of September and October. The disease is characterized by congestion of the ventral surfaces of the body, with more or less ulceration in, and haemorrhage beneath, the skin, bloating due to serous exudation into the lymph sacs, gradual failure to respond to stimuli, which symptoms are followed by coma and death, the last being occasionally preceded by tetanic seizures. After death haemorrhages into the muscles and degenerative changes in the muscles, spleen, liver, and, to a slight degree, in the intestinal tract, are found. The blood shows an advanced degree of anaemia and leucocytosis. Predisposing causes of the disease are lesions of the skin, which seem to be the usual portal of entry of the infection, and lowered resistance from heat and from anaemia. By a series of controlled experiments with inoculated frogs we have shown that, while temperatures a little above freezing have no harmful effect upon the frogs, they completely control all manifestations of the disease in inoculated or diseased frogs, if the frogs are left in the cold for a period as long as seven days; and, further, that even short periods in the cold chamber will bring about a delay of the fatal results in diseased or inoculated frogs. The anaemia so often found in apparently healthy frogs seems in many cases to be due to the presence in the lungs of the frog of a parasite, the Distomum cylindraceum, which, occurring in sufficiently large numbers in an individual frog, is capable of materially diminishing the available supply of red corpuscles. Severe laking of the blood, the presence of numerous isolated red-cell nuclei, and great diminution in the number, or almost total absence of the red cells in the diseased frogs, are in proportion to the severity of the infection and due to bacterial action. The presence of the haematozoan parasite, the Drepanidium, does not play any part as a predisposing or exciting cause of the disease. The ascarid Rhabdomena nigrovenosum, although frequently present as a parasite in the lungs of the frogs, plays no part in causing or promoting the disease.

19866986

1905-1909

A STUDY OF THE CHANGES IN THE BLOOD AND BLOOD-FORMING ORGANS PRODUCED BY CYTOTOXIC SERA, WITH SPECIAL REFERENCE TO HAEMOLYMPHOTOXIN.

The cytotoxins are not specific. (2) The changes occurring after the injection of different cytotoxins are similar and do not vary in kind. (3) The changes do, however, vary in degree in the following order, the one having the most marked effect being placed first, etc.: (a) Haemolymphotoxin, (b) Splenotoxin, (c) Lymphotoxin, (d) Endotheliotoxin, (e) Nephrotoxin, (f) Hepatotoxin. (4) Nephrotoxin causes the most specific change. (5) The haemolymph glands play some important part in the production of eosinophiles. The haemolytic action of haemolymphotoxic serum is greater than that of other cytotoxic sera. (6) The histological changes which are observed in every case are secondary to the haemolytic factor present in all cytotoxic sera.

19866989

1905-1909

COMPARATIVE STATISTICS OF ANTITOXIN HORSES. A STUDY OF THE RECORDS OF ONE HUNDRED HORSES IMMUNIZED TO DIPHTHERIA TOXIN, WITH COMPOSITE OF CURVES.

1. Better results in the production of diphtheria antitoxin can be obtained with greater experience in the selection of the most suitable type of horses to be used. Young animals are usually to be preferred. Over one-half of all such horses can be made to yield 300-unit serum, while a third will yield (5)oo-unit serum. 2. High-test horses require a shorter time to immunize and will yield a potent serum for a longer period than will low-test horses. 3. The period of usefulness of an antitoxin horse is short, and on an average endures only a few months. 4. A horse having attained a maximal antitoxic height begins to suffer a decline in antitoxin, which is usually as rapid as the ascent has been, and is unaffected by subsequent injections of diphtheria toxin.

19866992

1905-1909

A STUDY OF THE PROTECTIVE ACTION OF SNAKE VENOM UPON BLOOD CORPUSCLES.

Washed blood corpuscles of certain species of animals in a concentration of about (5) per cent suspended in salt solution containing above 4 per cent of cobra venom undergo changes in their resistance to certain physical and chemical agents. They become non-haemolyzable by water, ether, saponin, and quite strong solutions of lecithin, provided always that the excess of venom has not been entirely removed. On the other hand, certain acids and alkalis, excepting ammonia, lake the venomized corpuscles more easily than they lake normal corpuscles. Venom solutions of 2 per cent and less exert no protective property upon blood corpuscles, but they induce changes in the corpuscles whereby they are rendered more easily laked by the same physical and chemical agents.

19866994

1905-1909

SOME QUESTIONS RELATING TO THE VIRULENCE OF MICRO-ORGANISMS WITH PARTICULAR REFERENCE TO THEIR IMMUNIZING POWERS.

The virulent cholera spirillum possesses a greater number of bacteriolytic and agglutinable haptophore groups, or these groups are endowed with a greater avidity for uni- and amboceptors than the avirulent. The number or the avidity of the bacteriolytic receptors possessed by a bacterium is directly proportional to its virulence. However, the agglutinable receptors do not follow this law, that is, the agglutinable haptophore groups are not necessarily present in the same proportion as the bactericidal ones. While the energy of growth is a very important factor in relation to virulence, other phenomena must also be considered. The virulent organism possesses a greater number of toxic haptophore groups than the avirulent. The binding power of the free receptors of the organisms for bacteriolytic amboceptors in vitro is proportional to the bactericidal immunity produced in animals by each, which latter is in turn proportional to the virulence of the organisms from which the receptors were extracted. The binding power in vitro of the dead micro-organisms of different virulence for bacteriolytic amboceptors is not in proportion to their toxicity. The bactericidal immunity obtained by means of the inoculation with the dead organisms of different virulence, or their extracts obtained by autolytic digestion, is proportional to the virulence of the living strains of the bacteria employed. With the living organisms, while the bactericidal immunity obtained from the inoculation of animals with the virulent organism is greater than that produced with the avirulent, such immunity is not in direct proportion to the virulence of the bacteria introduced. These conclusions apply to the two strains of cholera spirilk employed in the foregoing experiments. Whether they will also hold good with other strains of this spirillum or for micro organisms in general, must be decided by further experimenta work.

19866996

1905-1909

ON THE HEXON BASES OF LIVER TISSUE UNDER NORMAL AND CERTAIN PATHOLOGICAL CONDITIONS.

The results above reported lead to the conclusion that while in the degenerating cells chemical changes are taking place tending toward a diminution of the hexon bases as a whole, they affect the arginin especially. One may picture the process either as a partial or as a complete breaking down of certain proteid. material more or less rich in hexon bases, leaving behind. proteid matter poorer in bases. The meaning of these changes is, however, obscure, and with the limited number of known facts bearing upon the subject, it would seem idle even to attempt to formulate an hypothesis to explain them. Certain work of other investigators is, however, suggestive in this connection. Kossel and Dakin, for instance, as illustrated by their work upon the simple proteid body clupein, found that a partial destruction of the proteid molecule, involving the arginin group, is brought about by a ferment furnished by the animal organism. When subjected to the hydrolytic action of a mineral acid, clupein yields arginin in considerable abundance. But if the clupein is first acted upon by the ferment arginase found in the liver, and then subjected to acid hydrolysis, the yield of arginin is appreciably diminished. Among the cleavage products in the latter instance are the components of arginin, namely, omithin and urea. It would seem, therefore, as if the ferment had loosened the union between the omithin and urea in the arginin group, so that upon subsequent hydrolysis a diminution of arginin resulted. In the cases studied by me, it may be that the conditions were favorable for some such ferment action as that above described, and hence the relatively low yield of arginin. No attempt, however, was made to ascertain if omithin were present in the urine. Its presence there would seem not wholly unlikely when one considers the diminished power of oxidation of the phosphorus-poisoned cell, although Thompson has shown that arginin or omithin when administered to a healthy dog as food or by hypodermic injection is eliminated for the most part as urea, no ornithin being found. There might seem to be a conflict between this view and the results recently published by Wohlgemuth, but it must be borne in mind that the influences at work causing the breaking down of the proteid molecule are probably quite diverse in character. Wohlgemuth has recently shown for the first time that a diamino acid may actually find its way into the urine in phosphorus poisoning. He found arginin in the urine not only in rabbits poisoned with phosphorus but also in a patient suffering from phosphorus poisoning. On the other hand, he was unable to find lysin in the urine. This fact is of especial interest in view of the evidence set forth in this paper that the arginin base is lost to the proteid molecule more rapidly than the lysin base. The correspondence between the findings in the liver and in the urine is thus a close one. How much of the arginin liberated from the proteid molecule may find its way into the urine is of course uncertain. It seems reasonable to suppose that a portion of the base is acted upon by the arginase ferment in the manner already described. Of the seventeen to eighteen cleavage products of the proteid molecule thus far isolated, the hexon bases are among the most stable. One or more of these bases have been found in practically all proteid matter thus far investigated; in fact arginin is so uniformly present that Kossel has made the suggestion that it is the kernel of the proteid molecule. At all events, the question may be asked, whether, if the influences at work in the altered liver tissue were of a general character causing a diminution of the hexon bases, the monoamino acid groups would not suffer even a greater diminution; and since the pathological condition is undoubtedly associated with impaired oxidation, their presence should not be expected in the urine. As a matter of fact, Ignatowski found considerable quantities of monoamino acids in the urine of patients suffering from gout, pneumonia, and leukaemia, though under normal conditions no monoamino acids were found in the urine, indeed, not even after the subcutaneous injection of glycokoll. Furthermore, the loosening of the amino acids from the proteid molecule is suggested by the fact that Taylor found such acids in the liver of a patient who died from a hepatic disease of obscure etiology, but which he was inclined to attribute to chloroform poisoning. Taylor found not only leucin and tyrosin in the liver, but also arginin, a fact not without interest in view of the diminished arginin content found in the livers of the chloroformed dogs after acid hydrolysis. Moreover, the falling off of the hexon bases under the conditions studied seems quite in accordance with some results recently reported by Levene. He has shown that certain cleavage products obtained by the action of mineral acids upon self-digested pancreas, spleen, and liver, are much diminished when compared with the products obtained from the fresh glands. The lysin and arginin of the digested liver, for example, showed a diminution of over 50 per cent. It is now well established that in course of the process of aseptic autolysis, the proteids of the liver cell undergo decomposition into simpler substances, and Jacoby showed that during life autolysis may go on in portions of the liver in which the circulation has been hindered. But of greater significance still in this connection, is the observation made by Jacoby on the autolytic changes in the liver during phosphorus poisoning. He found that when the normal liver substance is permitted to autolyse the solution of the liver substance is a slow one. On the other hand, under similar conditions the liver of a phosphorus-poisoned animal undergoes rapid and almost complete solution. The difference in the behavior of the normal and damaged liver points to an increase of normal ferment action in the case of the poisoned organ. It thus seems reasonable to suppose that in phosphorus poisoning we have during life an exaggerated breaking down of the proteid molecule associated with an over-action of certain ferments, and among them probably arginase. The pathological process in the liver during life may, therefore, be thought of as proceeding in the same general direction as the process of post-morten autolytic decomposition. By means of further studies along lines indicated in this paper, it should be possible to gain a deeper insight into numerous pathological processes. The changes in amyloid degeneration are among those which promise to be better understood through the application of the new methods of chemical analysis. Moreover, it cannot be doubted that pharmacology as well as toxicology has much to gain from a study of what happens to the proteid molecule under the influence of poisons.

19866999

1905-1909

ENZYMES AND ANTI-ENZYMES OF INFLAMMATORY EXUDATES.

The serum of an inflammatory exudate has the power of inhibiting the action of proteolytic ferments contained in the leucocytes. This anti-enzymotic power is possessed by the blood serum from which it doubtless passes into the exudate. In the later stages of inflammation there is some diminution of this anti-enzymotic action. The anti-body contained in the serum is destroyed by a temperature of 75 degrees C. The proteolytic ferments of the leucocytes act both in an acid and in an alkaline medium but are most efficient in the latter. The anti-enzymotic action of the serum is favored by an alkaline reaction, but is completely lost in an acid medium.

19867001

1905-1909

ON THE PRESENCE OF CERTAIN BODIES IN THE SKIN AND BLISTER FLUID FROM SCARLET-FEVER AND MEASLES.

In sections of control and normal skin, the nuclei of the epithelial cells were often indented by the cell protoplasm, giving them an appearance similar to those indented by Mallory's bodies. It would seem that if these bodies of Mallory's were protozoa they would have been found in the sections from both the living and the dead skin of scarlet-fever and measles, as they were present in the blister fluid. Their absence is certainly more suggestive of a degeneration than of a protozoon. This view is also borne out by the fact that they were not found immediately after death, but were present in another specimen from the same case removed twenty-four hours later. It would seem probable also that the bodies found in the blister fluid were the products of degeneration and cytolytic activity, because they were found in the antitoxin rashes as well as in the cases of scarlet-fever and measles. The histological changes in the skin of these two diseases leads us to expect the presence of cytolytic products both in the blister fluid and in the sections. It certainly cannot be stated that none of these bodies is a protozoön, but it can be positively stated that a great majority of them arise from degenerating cells; and in many cases, I think, it is not possible to differentiate a degeneration from a protozoön by the study of its morphology and staining reactions. The bodies present in blister fluid resemble very closely those granular bodies found in blood under certain conditions, and seen in vaccine lymph and in emulsions of tissues and in exudates. I think, therefore, that they are for the most part, if not wholly, products of degenerating tissue cells and of leucocytes, and within certain limits specific to scarlet-fever and measles.

19867003

1905-1909