INTESTINAL PUTREFACTION AND ALBUMINURIA. By John C. Hemmeter, M.D., Philos. D., etc., Clinical Professor of Medicine in the Baltimore Medical College. (CONCLUDED.) THE hygiene of the mouth is a most essential condition to prevent infection to a successive degree. Diseases of the upper air passages that cause catarrhal discharge and offensive breath should have the attention of the practitionercatarrh, polypi, adenoid growths, bony malformations, must be properly treated. Simple post-nasal catarrh is a frequent cause for filling the stomach with lumpy mucus, particularly during sleep. A very effective spray for this condition is the following: R.-Solution acid boracici saturat Listerini. Zinci sulphocarbolat Al Ziii Al Zi gr. xx M. Sig. Use in atomizer every three hours. It is a very common thing in these days to have apparently healthy individuals suffer with fetid breath. The teeth are generally in fair condition, the tongue not very coated; on inspection, however, it will be found that the mu. cous membrane of the buccal cavity is thickened, the teeth leave their impression upon the cheeks and tongue. It is not one of the objects of this paper to go into the symptomatology of the various forms of stomatitis and glossitis, but simply to emphasize the necessity of detecting and treating these conditions in renal and intestinal diseases. Miller has isolated more than one hundred different micro-organisms from the human teeth. McFadyen, Boas and others have identified a large number from the human stomach. According to Gillespie, many organisms can grow in the human stomach, although the degree of acidity may be very high, notably the bacillus lactis aerogenes, the colon bacillus and the pyogenic cocci (bacteria of the stomach Journal of Path. and Bact., Vol. 1, page 279). Entire abstinence from food does not eliminate the fermentative and putrefactive processes. In observations made upon Cetti, the professional hunger artist (Hunger Künstler), or faster, it was shown that while in hunger the excretion of indican was greatly diminished, that of phenol through the urine was markedly increased; on the eighth day of fasting it was five times as great as the amount eliminated normally. In animals the same has been observed. It is quite evident that the albuminous matters of the various intestinal secretions furnish a medium upon which the intestinal bacteria may thrive and from which they can produce their peculiar products. Pisenti (Jahresberichte f. Thierchemie, Band 17, page 277) found that ligation of the pancreatic duct causes at once a diminution in the excretion of indican and that the feeding of pancreatic juice or pancreas peptone caused this excretion to increase at once. One is justified in concluding from the effect of fasting on the relative output of indican (reduction) and phenol (increase) in the human subject that the food stuffs furnish the bacteria with material from which they form indican, but in the absence of food the albuminoids of the various intestinal digestive juices furnish the material wherewith they form phenol. The nature of the atmosphere in the intestine, the almost absolute absence of oxygen, is a condition under which only anaerobic or facultative anaerobic bacteria can grow. Among the long list of pathogenic bacteria of the intestines the pyogenic cocci are frequent and prominent factors. The unformed ferments produced by the cells of our digestive glands are chemical substances and to a great degree resistant to the deleterious action of poisons that would destroy the cells which produced them. These unorganized digestive ferments after they are once produced them. produced are not dependent upon the life of the cell that generated them. The activity of the formed ferments or ferment organisms, however, is intimately associated with the life of the cell that produced them (i. e., if it be an accepted view that the ferment in case of bacteria, yeast, etc., is something different from the bioplasm of the bacterial cell), at least anything that interferes with the fermentative process. It is, I believe, a well founded opinion, that the products associated with any given fermentation process are simply the excretory or metabolic products from the cells' growth (Chittenden ). Probably in many cases, if not in a large number, the formation of a true enzyme is the first manifestation of chemical activity whenever the microorganism begins to develop in its culture medium, the products resulting from the action of the so formed enzyme being eventually broken down into simple products by the cellular activity of the microbe. For instance, moist blood fibrin that has stood in contact with the air for some hours, then placed in water at 40° C., will in the course of a week become totally liquified under evolution of offensive gases and ultimately be converted into carbonic acid, water, ammonia and sulphuric acid. But when, on the other hand, the moist fibrin is placed in chloroform water (germicidal) instead of ordinary warm water, after weeks the fibrin disappears as before, but no gaseous products are formed and the fibrin is simply converted into soluble proteoses and peptones (with traces perhaps of leucin and tyrosin). This is done solely through the influence of the enzyme formed by the bacteria before coming into contact with the chloroform water. The more profound changes due to activity of the microorganisms, by which simpler products result, are entirely absent, due to the antiseptic action of the chloroform. Here the enzyme action is very much like the action of ordinary digestive enzymes and the products formed are identical. The typical putrefaction and fermentative products owe their presence to the continued life and activity of the micro-organisms. This being destroyed, fermentation does not occur, but the enzyme once formed continues its action wholly independent of the cell from which it originated. Whilst the particular micro-organism can produce their characteristic metabolic or secretory products only in that atmosphere which is best adapted for its growth and development, the enzyme will act equally well in the presence or absence of oxygen. Ferni (Archiv f. Hygiene, Bd. 10, page 1, Bd. 14, page 1) has found proteolytic and diastatic enzymes in a large number of micro-organisms. Both were discovered and in some instances isolated from Koch's vibrio, micrococcus prodigiosus, bacillus millerei, bacillus subtilis, bacillus megaterium. The trypsin,like enzyme, has been discovered in a large number of different forms of both bacteria and fungi. Under ordinary circumstances, the enzyme action due to bacteria is of small amount, since it is slow in contrast with the proteolytic or amylolytic action of the normal digestive ferments. Under physiological conditions, intestinal fermentation is undoubtedly held in check by a variety of circumstances, among which may be mentioned, perfectly normal digestion, healthy peristalsis and absorption, and antiseptic action of food stuffs. Concerning the latter point it should be emphasized that carbohydrates by their undergoing acid fermentation in the intestine, forming free lactic and acetic acid, are indeed antiseptic thereby in the real sense of the word. Further diminution of the proteid food must necessarily lead to a decrease of the aromatic fermentation products, therefore non-nitrogenous diet causes a decrease in the elimination of the combined ethereal sulphates. Brieger has proven by culture of intestinal bacteria in gelatin that they are capable of producing ptomaines. Baginsky and Stadthagen isolated from the rectal passages of cholera infantum a bacterium which after growing on sterilized horse flesh for ten days produced an albumose or pepton-like substance of intense toxicity. (Finkler and Stadthagen "Ueber giftige producte 1 saprogener Darmbacterien," Berlin. Klin. Wochenschr., 1890, page 294). W. D. Booker gives a concise account of the occurrence of proteus vulgaris in the gastro-enteritis of infants and the relation of the frequency of this bacterium to the severity of the disease (W. D. Booker, A Bacteriological and Anatomical Study of Summer Diarrheas of Infants, Johns Hopkins Hospital Reports, Vol. VI). According to this author a proteid substance has been obtained by Vaughan from beef tea cultures of proteus vulgaris which causes active vomiting and purging and finally death when injected under the skin of young animals. To resume the treatment of these intestinal fermentations and putrefactions, there is, as far as I can judge, much diversity of opinion regarding the antiseptic treatment of such diseases as typhoid fever, cholera and dysentery. With cholera I have had no experience, but dysentery has frequently come under my observation, and I have repeatedly attempted its antiseptic treatment. It seems impossible to obtain a clear idea of the efficacy or even expediency of this treatment because it is not possible to carry it out without applying to the case the rules of diet. The antiseptic chemicals employed in these treatments (Woodbridge treatment of typhoid) are in themselves not sufficient to produce improvement in the symptoms of auto-intoxication, but diet alone without internal drugging is frequently per se sufficient for this purpose. It is obvious that the more digestible the food stuffs injested, the less tendency there will be for intestinal fermentation, but the accumulation of indigestible material constitutes a condition after which fermentation is inevitable. It would be a most beneficial thing for everybody to put himself upon a rigid milk diet for three consecutive days every month. Its ready digestibility when properly taken is only one part of its beneficial action. Gilbert and Dominici (Comptes Rendu d. Societé de Biologie, April 14, 1894) have shown that a milk diet exercises a remarkable influence upon the number of bacteria present in the feces of man and animals. They made their studies upon a healthy man whose diet for five days consisted in part of 2.5 liters of milk per day. The feces of this person on an ordinary mixed diet contained 67,000 bacteria per milligram. There was a reduction of the number of bacteria on the second day to 14,000 per milligram and on the fifth day to only 2,500 per milligram. By the use of sterilized milk the number was still more reduced. Winternitz has shown that milk diet tends to greatly diminish the excretion of combined ethereal sulphates in the urine and that the feces contain neither indol, skatol nor phenol. It is not implied that it is the indican or the urea, uric acid or the combined or ethereal sulphates which exert this influence; these substances are good indications of the toxicity of the urine and they can and they can be readily determined. These substances are more or less poisonous if they pass through the kidney in excess, but it is possible that the most poisonous urinary constituents are more subtle substances which as yet escape accurate analysis, but which it is believed generally accompany an excess of the above mentioned bodies. most important support of the view that the toxines of intestinal putrefaction may produce such detrimental changes in the renal epithelium as to cause albuminuria would naturally be the experimental production of abuminuria in animals by injection of isolated toxines, or feeding the same. A The hypodermic injection or feeding of ethereal sulphates to animals would have to be carried on for some months most likely, during which period the animals would have to be confined. The experiments would be very expensive and on account of daily hypodermic injections present unsurmountable difficulties, particularly as regards control, supervision and the necessary weighing and analysis of the food. In guinea pigs I have observed that injection of 50 c.c. of urine showing a high ratio of the preformed to the combined sulphates will in 30 to 45 minutes cause albumen to appear in the urine of the animal. This excretion of albumen may persist for 12 hours after the injection. This will occur regularly every time the urine is injected while the ratio is high, but will not occur when the same ratio is made low by placing the patient on an exclusive milk diet. All efforts tending to explain how, or in what manner, auto-intoxications of the intestinal tract can produce poisoning of the renal epithelium must in the present state of our knowledge be conjectural. In fact, the literature on this particular subject is very limited, but it seems probable from the work of Hoppe Seyler and his school (Hoppe Seyler, "Beitrage z. Kenntnis d. Stoffwechsel bei Sauerstoffmangel." Festschrift z. R. Virchow's 70 Geburtstage) that one of the ways in which these toxines act is by reducing or inhibiting cellular (respiration) oxidation. Any toxines causing deprivation of oxygen from the processes of the intermediate metabolism bring about albuminuria (Avaki Zeitschrift f. physiol Chemie, Bd. 15, S. 335, B. XVI, S. 453, B. XVII, S. 311. To repeat, in concluding, the most essential features in treatment of renal insufficiency of this character, I estimate their importance in the following order: 1. A carefully selected diet adapted to the digestive peculiarities and powers of the individual. 2. Thorough daily evacuation of the gastro-intestinal tract. 3. Treatment of any gastro-intestinal disease or disturbances of metabolism. 4. The use of plain water as a food and stimulant to renal function (diuresis). 5. Maintenance of a healthy function. of the skin (diaphoresis) by daily adapted baths. 6. Strictest avoidance of mental exercise, insisting on rest to the nervous central organs and moderate physical exercise adapted to the special requirements of the case. CLINICAL HISTORY OF TWO CASES. Dr. H., teetotaler, aged 36, married, weight 138 pounds, has always been well barring occasional periods characterized by abdominal pain, distention, intestinal flatulence, loss of appetite and general malaise, a period of constipation lasting two days, preceded, as a rule, an attack of membranous dysentery. In 1891, when he first consulted me, he had been suffering at intervals with membranous colitis, which was accompanied by occipito-frontal neuralgia and intense rheumatic pains in both shoulders, particularly the left, and running down into the hands. His diet was of a mixed character and restricted to a moderate use of sweets, pastries, etc. About October 3 he was troubled with obstinate constipation, intestinal flatulence, pain and a sense of abdominal fulness after meals. On October 5 he had four copious dysenteric stools, very offensive in odor and containing large quantities of mucus and what are termed membranes; severe headache, rheumatism in both arms and insomnia. An examination of the urine collected during twenty-four hours on October 5, 1891, gave the following results of analy sis: Preformed sulphates (from norma! metab proteids) 1.926 grammes; combined or ether sulphates (from intestinal putrefaction) 0.236 grammes; ratio, 7.7; indigo blue, very strong; uric acid, 0.440 grammes; urea, 20.990 grammes; albumen, none; tube casts, none. Here we find a high percentage of combined ethereal sulphates, with great excess of indigo blue and normal uric acid ratio. During November, 1891, the doctor's colon was washed out daily with warm water and his diet for one week restricted to sterilized milk. The abdominal pain and flatulence wore away and sleep became normal. There is no record of putrefactive products in the urine during November, 1891. On December 10 the doctor committed an error of diet and on the next day felt very sick, had intestinal flatulence, no appetite and rheumatism in the left shoulder and also in the right foot. He was put upon egg albumen and brandy and his stomach and colon washed out. His urine showed the following on December 11: Preformed sulphates, 1.433 grammes; combined sulphates, 0.149 grammes; indigo blue, strong; ratio, 9.6. From this time on, doubtless in consequence of the restriction in diet, the ratio of the sulphates fell and remained for some time normal. The doctor felt weak, but was free from abdominal pain and had no rheumatism. He objected against his restricted diet and craved substantial food, as he said, and argued he needed strength and could not obtain strength from egg albumen and milk solely. Giving in to his continual solicitations, a diet of milk, meat, soft boiled eggs and bread was allowed. The possible bad consequences of such a diet are not derived from the diet itself if strictly adhered to, but that it encourages the patient to enlarge his menu upon his own responsibility. During December, 1892, January, a high percentage of combined sulphates in his urine and the indigo blue reaction was very strong after the acute symptoms had passed away. He was given high colon injections of olive oil after a previous cleansing enema had removed the feces from the colon. These oil clysmata exerted a most comforting. effect and for over a month the doctor observed no membranes in his stools. The following shows the results of analysis of his urine during January, February and March, 1892. (See Table.) During the time in which the oil clysmata were used and for six weeks thereafter when no mucus or membrane were in the stools, the indican disappeared. from the urine and the patient was free from rheumatism. Up to this time and February and March, 1893, there was little actual improvement; the hoped-for strength which the sufferer had expected from his increased food supply did not come; he continued to have flatulence, headache, rheumatism and general debility. It is noticeable that the indigo blue was obtained in that period in large amounts. On March 6, 1892, the patient's condition was worse than it had been since November 5, 1891. He had eaten raw oysters the day before and twenty-four hours later began an attack of membranous dysentery. He was given a grain of calomel every hour and egg albumen and brandy. He had severe rheumatic pains for four days, during which the stools were very offensive. During this period there was to the end of 1892 no albumen was ever found in the urine. During 1893 I saw the patient, perhaps a dozen times, as he was mostly traveling for recreation. He wrote occasionally and about July, 1893, reported that he was suffering from nervous dyspepsia and hyperacidity. During his travels it was difficult for him to carry out a strict diet, nor could he use his colon irrigations, as he was advised, two or three times a week. After having been almost cured for six months and his weight increased by twenty pounds on a restricted diet, financial losses brought on a condition of neurasthenia, which had as an accompaniment gastric hyperacidity. He returned about January, 1894, but did not report for treatment until February 22, |