that such bacterial invasion does not, as a rule, cause infection. In health they tend to be destroyed very soon after their reception. "The evidence of this," he states, "is now overwhelming." Ford investigated the bacteriology of normal tissues and organs. He was able to cultivate a great variety of organisms from the livers and spleens in 80 per cent of the rabbits, guinea pigs, cats and dogs he examined. Adami, speaking of this work, states that "Ford in general obtained no growths within three days. Evidently the bacteria in the organs are attenuated so that their growth is feeble and it is arrested until the bactericidal substances of the organ have become inert. These observations prove conclusively that bacteria are constantly entering the organism. But the bacteria thus introduced are very rapidly removed by the endothelial cells lining the blood vessels, especially those of the spleen, kidneys and liver, so that while the tissues of the healthy body are not of necessity free from microorganisms they are potentially sterile." It is also to be observed that this entrance of bacteria, according to Adami, may take place not only through the alimentary tract, but through the respiratory system as well. These fundamental observations showing that pathogenic bacteria are so commonly present in organs without producing lesions emphasize strongly the old truism that for the production of disease two factors are necessary-bacteria and the patient. Just as the pneumococcus grows on an agar slant but does not grow on potato medium so the pneumococcus multiplies in some individuals while in others it dies out. In many cases the different results depend upon the patient's so called resistance and a complete understanding of the process awaits the gradual unraveling of the mysteries of immunity. In other cases the factors are not so complex, and here the simpler observations of animal experimentation together with the pictures of pathological anatomy assist our explanation. The influence of trauma upon the localization of bacterial infection is one of our best known examples in this connection. The pioneers in bacteriology emphasized with right, the influence of points of least resistance in the development of disease and they have recorded an immense number of observations along these lines. We all know that if we injure the joint of a rabbit and then introduce pyogenic bacteria into his circulation the animal will almost invariably develop a purulent arthritis, whereas a normal control animal injected similarly has a chance of escaping without joint involvement. More recent work along these lines has also brought out rather unexpectedly as it were, the fact that trauma may play a more important role in certain diseases than has hitherto been suspected. The work of Tarozzi and of Canfor is especially interesting. These observers hay noted that animals can be injected intravenous with tetanus spore, and show no untoward symp toms. If, however, the animal is subjected to slight traumatism of skin sufficient to produ a blood clot or a small area of necrosis it di presently with the symptoms of a well develop tetanus. Here obviously the local injury allow the organisms to settle in the part, prolifera and elaborate their specific toxins which produ the disease. As important as these physical traumata a we must remember, however, that we may hay a chemical trauma as well. This phase of t subject is not nearly so well understood, when our ideas of chemical trauma have reach the clearness of our ideas on physical trauma, will at least have advanced far in our und standing of focal infections. Much interest has been aroused of late, c cerning the possible relationship between for infections and the development of gastric ulce Letulle, who found a gastric ulcer in a man su fering from dysentery, isolated the dysente bacillus from the stools and found that whe pure cultures were injected into guinea pig typical gastric ulcerations followed. Chan messe and Widal also produced typical gast ulcers by introducing dysentery bacilli direc into the stomach. Letulle also produced gast ulcers with cultures of staphlococcus, Bezan and Griffon with cultures of pneumococcus, Enrique and Hallion with diphtheria toxin. M recently in this country Rosenow has descri gastric ulcerations in animals which were injec with cultures of streptococcus. These observations on the probable bacte origin of many gastric ulcers seems at glance to conflict with the views advanced m years ago by Virchow and since his time tau by many pathologists. Virchow's idea of gas ulcer was that it was commonly a process embolism and thrombosis of the stomach teries with subsequent infarction and nec of the stomach wall. These views found tional support in the experiments of Cohnhe who produced infarctions and ulcers of stomach wall by injecting lead chromate the gastric arteries. A microscopic study, however, of the ul produced by bacterial injection shows that many cases there is a bacterial embolus pres in the process. Thus it has been proved t Virchow's ideas in many cases at least, w fundamentally sound. There still remains, however, another fac to be explained, by certain patients who are o stantly swallowing pathogenic bacteria, or h bacteria circulating in their blood stream a presumably in their gastric arteries, fail to 'velop gastric ulcers. Here the answer suggested by Bolton's work upon ulcer of the stomach. Bolton injected animals repeatedly with extracts of gastric mucosa and in that way produced what might be termed a gastro-toxic The serum when injected intraperitoneally into normal animals produced typical gastric ulcers. He found, however, that if the stomach contents were neutralized with sodium bicarbonate at the time of the injection no ulcers developed. Conversely he showed that if the acidity of the gastric juice was increased by the administration of acids, injection of the gastrotoxic serum produced more severe ulcers than in the controls. Bolton's conclusions as the result of his experiments and the microscopic study of the tissue, were that the gastrotoxic serum produced a necrosis of the gastric cells which allowed the gastric juice to digest an area in the stomach wall. If we substitute for the sero toxic necrosis a bacterial necrosis, we have an excellent example of pathological lesion produced by a combination of bacterial infection with a chemical trauma. This suggestion does not, of course, appeal so strongly in the uncommon cases of gastric ulcer with anacidity, but it would seem to apply in the vast majority of cases where there is still an acidity present either increased, normal or diminished in amount. The relationship between bacteria and appendicitis seems to be as definitely established as almost any fact in medicine. We have all been familiar since the classic paper of Fitz with bacterial infection of the appendix, the acute inflammation followed by pus formation and rupture with a local or general peritonitis. Just why, however, this process occurs in some individuals and not in others is a question which is still a subject of lively debate. We are all familiar with the long-taught idea that in some way the lumen of the organ becomes occluded and that the bacteria which are in the habit of wandering at will in and out of the appendix become enraged as it were, at this infringement of their personal liberty and begin to viciously attack the appendiceal mucous membrane. Expressed scientifically we read that occlusion of the lumen with retention of the contents lead to a multiplication of the bacteria with an increase in their virulence. In many cases fecal concretions or foreign bodies seem to produce the occulsion of the lumen. Many undoubted instances of occlusion due to intestinal worms are reported and we have recently seen an appendix removed at operation which contained an ascaris worm. This idea of the role played in appendicitis by foreign bod es has been so dramatically described by the press that we often meet individuals who in eating grapes carefully pick out all the seeds and put them on one side of their plate, making meanwhile a sagacious remark about an ounce of prevention. That appendicitis may result from bacteria passing out from the lumen into the wall of the appendix seems fairly definitely established. And in such cases microscopic examination of the appendix shows erosion and necrosis of the mucous membrane with a gradual extension of the process outwards. In these cases if we do find fecal concretions or foreign bodies in the appendix we have an excellent example of bacterial infection combined with a mechanical trauma. Very often, however, our friend who carefully deposited his grape seeds on the side of his plate comes down much to his amazement with an attack of acute appendicitis. At operation a large inflamed appendix is removed which, however, on being opened shows no fecal concretion nor even a grape seed. And then some surgeons are puzzled as was the patient. A careful microscopic examination of this appendix shows that the mucosa is intact, nearly normal, and that practically all of the pathological changes are in the wall and increase in intensity as we pass outwards to the serosa and meso appendix. In this case the infection has been obviously from without, through the bloodstream-in other words an embolic proces. This idea that many cases of appendicitis are embolic in origin is constantly gaining ground among pathologists and surgeons. And in this group we look for and frequently find foci of infection elsewhere. In our own limited experience several cases can be recalled in which this type of pathological picture was associated with foci of infection in the teeth and tonsils. Many surgeons of large experience doubtless recal! many instances. One observer particularly, Kretz, has emphasized this point of view and has even gone so far as to record his opinion that most cases of appendicitis are due to infected tonsils. Recent bacteriological studies would seem to lend additional support to this idea. Aschoff and his students find gram positive diplococci and gram positive bacilli as the etiological factors. The oft repeated statement handed down from text-book to text-book that the colon bacillus is the most commonly found organism need not disturb us, since it might be remarked that any bacteriologist failing to grow a colon bacillus from a diseased or even normal appendix, must be working with an exceptionally poor lot of culture media. In these cases of embolic appendicitis, many factors may aid the bacteria in localizing in the appendix. The fecal concretions may produce an erosion which allows an initiation of the process, or kinks in the bowel may interfere so much with the circulation as to aid in this local ization. Personally I have frequently been impressed by cases of appendicitis occurring after the patient was markedly fatigued. Here a possible analogy is suggested to the experiments of Charrin and Roger who found that the susceptibility of rats to anthrax infection was markedly raised after the animal is fatigued by running in a treadmill. In diseases of the liver apart from definite pyogenic processes, evidence is constantly accumulating to prove the role played by bacteria. Nicholls and Ford, as previously mentioned, have shown that livers in health contain bacteria and it seems reasonable to assume that in patients with foci of infections the bacterial content would be increased. This idea, too, has been seized upon by enterprising journalists who have told the lay press that the liver is nothing more nor less than a big bacterial filter for the human body. This statement with limitations may be accepted as approximately correct, but what interests medical men most is why this big bacteriological filter gets clogged up. Hektoen, Weaver, Abbott and others have described liver lesions often simulating closely a hepatic cirrhosis, following the injection of bacteria. The production of cirrhosis in their experiments were, however, on the whole, rather inconstant, and the lesions most frequently produced were simple areas of necrosis. Opies classes well known experimental production of liver cirrhosis with chloroform and colon bacilli has advanced our conception of this process. Also it has emphasized again the important correlation between bacteria and trauma - the trauma here being chemical and consisting of a chloroform necrosis of the liver. In our laboratory it might be mentioned that large pyogenic abscesses of the liver were produced by first damaging the liver tissue through subcutaneous administration of phosphorus and then injecting staphylococci intravenously. Opies' work, of course, opened up a fresh discussion as to the role of alcohol in the production of hepatic cirrhosis. Many pathologists have expressed the view that in cirrhosis the alcohol acted only as a chemical trauma, while certain clinicians, skeptical and wisely so, perhaps, have still clung tenaciously to the alcohol per se theory. Perhaps it would be well to declare a truce just now between pathologists and clinicians and leave the question to be settled by the next generation living under universal bone-dry laws. Investigations into the causation of diseases of the kidney, especially chronic nephritis, have in the last few years received much stimulus from bacteriological investigations. Chronic nephritis, a disease which annually exacts death toll off over 60,000 in this country, has long been regarded as one of the diseases of obscure causa tion. Many factors involved in its causation re main still undeniably obscure, but out of the obscurity many flashes of light are coming. The role played by lead in the production chronic nephritis in painters, has been recognize by physicians for nearly a century. Since, how ever, painters do not have a monopoly of chron nephritis other causes must be at work. In search for other cases laboratory workers this and other countries have made contribut of lasting interest and worth. The workers in this field began first to c periment with chemical poisons, and we kno from the brilliant investigations of Dickson Christian, Brown, Baehr and Ophüls that es quisite pictures of both acute and chronic phritis can be produced by injecting into animal repeated doses of such substances as uranium nitrate, potassium bichromate and iodine. Th work has been especially valuable in showing that chemical substances which damage the ki neys and produce acute nephritis after a sing injection will, if repeatedly injected, induc chronic nephritis. Further laboratory work done along similar lines, using bacteria or their products instead of chemical poisons, has also added to our knowl edge of the etiology of chronic nephritis. The relationship between infectious diseases and acut nephritis was appreciated by the earliest work ers in bacteriology. Thus we find Kannenber as far back as 1880 emphasizing the relationsh between acute nephritis and tonsilitis and 1884 we have a dissertation by Ernst describi two cases of acute nephritis associated with pr monia in which he demonstrated bacteria microscopic sections of the kidneys. In 18 Mannaberg produced acute nephritis in rabb and dogs by the intravenous injections of strept cocci which he obtained from the urine of tients with acute nephritis. Mannaberg belie that these streptococci were specific organist and affected the kidneys electively, and in work we see the idea of the selective affinity streptococci which has had such an influe upon our ideas of infection. Studies, however, showing a relationship. tween bacteria and chronic nephritis are of m recent origin. A number of papers have peared recently in which the typical lesions chronic nephritis were produced by the expe mental injection of micro-organisms. Bailey reported chronic nephritis following repeated jections of colon bacilli, Klotz has describ similar results after injections of streptococci Winternitz and Quinby have produced chro kidney lesions following the injection of cultu of B. bronchosepticus directly into the ret arteries of dogs. Our own work has shown th cultures of B. mucosus capsulatus induce li changes in the kidneys of animals. We have present a culture of the B. mucosus capsulatus a single intravenous injection of which produces an intense acute nephritis, while repeated injections give rise to a chronic nephritis, with albumen and casts in the urine. An interesting microscopic finding in our experiments is the marked damage to the glomerular apparatus which is in harmony with the pathological findings in cases of human chronic nephritis. The interesting question also as to whether the toxins of bacteria are of themselves able to produce chronic kidney lesions, was studied in another series of experiments. And here we found that the repeated injections of killed S. Sureus cultures would produce chronic nephritis in animals which had previously received a minute dose of uranium nitrate. In our experiments with the B. mucosus capsulatus, however, the interesting fact was noted that the degree of chronic nephritis produced was not always dependent upon the number of bacilli injected nor altogether upon the number of injections given. Animals show marked individual variations in their response to the bacterial injections. A further intensive study of this problem of individual variations promises to aid in clearing up the etiology of chronic nephritis. And here the old thought of trauma combined with bacterial invasions recurs. O'Hara has shown that animals injected with uranium nitrate and colon bacilli show far more damage in the kidneys than animals injected. with colon bacilli alone. Here we have a chemical trauma added to bacterial infection, but it may be objected that uranium is a specific kidney poison and also that it rarely gets into the * circulation of man or animal unless experimentally introduced. Some evidence is, however, accumulating which suggests that a disturbed body metabolism may secrete toxins which damage the kidney. Every clinician knows the bad effect of an excessive protein diet in certain cases of chronic nephritis. Longcope has shown that the repeated injections of egg albumen in animals will produce chronic kidney lesions. Salant has found that different diets cause marked changes in an animal's resistance to nephritis experimentally induced by certain chemicals. Thus, for example, he found that rabbits, when fed carrots resisted much larger doses of tartrates than did rabbits which received oats and cabbage. Also he found that carrots seemed to protect rabbits to some extent against doses of zinc malate. Ellinger has also found that cantharidin fails to cause nephritis in animals fed on a carrot diet. The explanation of these interesting findings is still being sought. Salant suggests that the work of Metchnikoff and Wollman may offer a clue. These two workers found that indol form ation is inhibited by a diet of carrots. It is also possible that cresol and phenol formation is likewise inhibited and these two substances as is well known are severe renal irritants. In summarizing these observations up on several disease conditions having a close relationship to foci of infection, it might be remarked that in our vigorous pursuit of offending microorganisms important as it is, we should not neglect the factor of trauma-as aiding these organisms in firmly intrenching themselves. Studies along these lines are urgently needed and will unquestionably shed much light not only upon the problems of etiology but upon those of therapy as well. THE BOY: A LAYMAN'S PSYCHO- GUY BOGART, Los Angeles, Cal. (Perhaps a layman's ideas shouldn't creep into the learned pages of the medical press. But as the son, nephew and grandson of physicians, not to mention an ancestry of medical and surgical men dating back to the earliest colonial days, I feel a peculiar interest in the journals of the profession.) With the coming of fatherhood many of the problems of my own boyhood days have become clearer. Father stands out in a clear light now. Not that I have become suddenly wise; rather my deepseated ignorance has been revealed. But early my wife and I decided that prophylaxis and hygiene are better than all other precautions. So Robert has passed through four and one-half years with but two direct passages with the surgeons once when the stork needed the man of science to officiate at his function and later when the sidewalk proved harder than bones and tendons. What a questioning little question mark these protean sparks of soul-stuff in growing humanstuff encased. I have expressed the wonder in my little PROBLEM OF THE BOY I seek solution of a problem. See how the shuttles of fate In interplay Of forces varied to produce What of Heredity? The long stretched lines Of the warp, Gift of the misty past to What of Environment, Potent in moulding A tired mother, Hungry and tired, He is born into the world. Still underfed, grows into Hopes and longings Burn in that abysmal home, And bright pictures of the future. Steadfast beckon to The boy. The boy in the home. How he wins his way into the deepest roots of love. Do you recall, of course you do, such scenes as HOLDING BOBBIE'S HAND A little hand at night, Reached from Bobbie's bed, Clasped tight in mine, And a little laddie all sleepy and tired, The sandman story has been read, And the good-night kiss bestowed. And editors to satisfy; A new book, perhaps, or favorite maga |