THE TRUE VALUE OF PICRIC ACID AS A TEST FOR ALBUMEN AND SUGAR IN THE URINE.

THE TRUE VALUE OF PICRIC ACID AS A TEST FOR ALBUMEN AND SUGAR IN THE URINE.

1083 and the patient got rapidly ill again ; the temperature was 103°, the pulse 110, the respiration 32. The tongue was loaded and dry, and there wer...

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1083 and the patient got rapidly ill again ; the temperature was 103°, the pulse 110, the respiration 32. The tongue was loaded and dry, and there were signs of fresh consolidation in the middle of the right back. The lower part of the right lung remained much the same as before. An alkaline saline was ordered every four hours, with brandy, quinine, and poultices. On April 2nd the said he was well, and the skin was moist. There patient Within were moist crepitations over the right lower back. - four hours of the time at which these notes were made the and there were pulse and temperature had risen rapidly, signs of renewed illness. Cough set in for the first time ; the face became bluish. The signs of a third strip of consolidation were detected higher up in the right back. The brandy was increased in quantity, and ammonia was added - to the medicine; hot bottles were applied to the extremities. Again, on April 3rd, the patient was better; the temperature had fallen to 96° ; the pulse was 80, but very weak and small. In the evening the temperature was 103°, and the consolidation had extended upwards. The notes of April 5th speak of improvement, but towards the evening the chilled, and all the symptoms grew bad patient suddenly again. The next morning the temperature was 97°, hut at noon a sudden severe and prolonged rigor occurred. Strong soup and other stimulants were persevered with. There was now dulness on percussion at the base of the left lung ; the skin was cold at the extremities, though everywhere ,dry. Another rigor occurred on April 7th, and afterwards on each day at half-past twelve there was a rigor till the llth and 12th, when none occurred. At midday on the 13th another rigor supervened, and the patient was much ex’hausted; there were large crepitations to be heard at the base of the left lung. On the 14th he passed a fair night, and the temperature was 96° ; there was an occasional cough and a slight amount of viscid, unstained mucoid expectoration. At midday the worst state of the patient was reached; the skin became dusky, dry, and hard, with a severe rigor; the pulse was small, weak, and irregular, and he had the aspect of one suffering from cholera. He remained in this state about four hours, and then began to recover at about five P at. The urine contained a little albumen ; there was no cough and no expectoration. The pulse was 116, compressible and irregular. There were the signs of consolidation of the upper part of the left lung. On the 15th he improved till the evening, and on the 16th he was greatly better. Later on the physical signs were clearing up, and the temperature was 98° in the evenings. The diet was changed to semi-fluid articles, and claret was allowed. On the 6ch May the patient was fully convalescent, and complete recovery soon followed. The patient had passed througti a,3 many as nine or ten severe rigors with six pneumonic consolidations and seven weeks’ illness. In his remarks on the case Sir Andrew Clark spoke of the Temarkable character, assemblage, and progression of the symptoms, and of the age of the patient, making the case one of - great rarity in the annals of medicine. The nature of pneumonia, whether it were a local disease or a fever with a local manifestation, was touched upon. If pneumonia be really an inflammation or not was a question which had concerned him for many years. In his work on pneumonia Dr. Sturges considered that the phenomena of inflammation were conspicuously exhibited in pneumonia, and that the anatomical and histological phenomena were fully satis-fied. Further, he not only considered pneumonia to be inflammatory, but regarded it as the pattern and model of all inflamma.tions. Sir Andrew had contested these views at the Royal College of Physicians as long ago as 1866. In a consolidated pneumonic lung we might histologically investigate the solid exudation in the alveoli, the relations of the exudation to the alveolar wall and the condition of the alveolar wall itself. In investigating these three conditions he failed everywhere to find any signs of cell proliferation, and there were nothing but the signs of regressive change. The number of red discs extravasated in acute pneumonia equals or exceeds the number of leucocytes; the blood-discs were undergoing changes in the fibroid network just as in blood-clots. In the alveolar septa there was no evidence of any change with the exception of occlusion of some of the bloodve-sels. Dr. Johnson had shown that in acute nephritis the vessels were not occluded but much enlarged The absence of sins of active cell proliferation made one ask whether the alveolar tissues might not be incapable of any other manifestation of the inflammatory process. But the facts observed after traumatic influences, in connexion

with tubercles and as a result of inhaled irritant particles, from the spread of inflammatory processes from the periThese concardium or pleura, negatived such a notion. siderations made him believe that the consolidation of pneumonia, though it might be an abortive inflammation, was much more like an active congestion in which capillary extravasation took place before the inflammation could be continued to its classical completion. With regard to the principles which guided him in treatment there were possibly none, and medicine might be said to be the most unprincipled of arts, and that every case was a law unto itself. He had given, first, attention to the man, and next to the malady. The food was given in relays, not too liberally nor too frequently. He endeavoured to maintain the vigour of the circulation, and by other measures, such as warm spongings, the maintenance of gentle evacuations, the absence of noise or fussiness, with light and fresh air to keep the organism in the best possible state for recovery.

rigor was observed,

or

THE TRUE VALUE OF PICRIC ACID AS A TEST FOR ALBUMEN AND SUGAR IN THE URINE. BY GEORGE

JOHNSON, M.D., F.R.S.,

PROFESSOR OF CLINICAL MEDICINE, SENIOR PHYSICIAN TO KING’S COLLEGE HOSPITAL.

RATHER more than two years ago the discussion on the of picric acid as a test was commenced in the pages of THE LANCET. The object of the present communication is to summarise the result of that discussion. And first, I beg sincerely to thank those who frankly stated what they believed to be objections to the test, for the result has been that its true value has been more speedily and firmly established than it could have been if it had been left unnoticed and uncriticised. The objections to its use as an albumen test have been the following :1. It was said that it gives with peptones a precipitate not distinguishable from albumen. It is a fact that it gives with peptones a precipitate at first sight like albumen, but I was the first to show that the peptonous precipitate, unlike the albuminous, is completely redissolved by heat much below the boiling-point of water. Now, this power of precipitating peptones when mixed, even in very minute quantities, with urine constitutes one of the chief uses of picric acid as a test. I have always insisted on the importance of applying a boiling temperature to every urine in which picric acid throws down a precipitate. Such a precipitate, if composed of albumen, is always made more dense and voluminous by beat; while, on the contrary, a peptonous precipitate entirely disappears, and one of mixed peptones and albumen is lessened by heat. The result of this extremely simple and accurate mode of testing for peptones has been that I have found them in only two out of several hundred specimens of urine. The often repeated statement that peptonuria is of frequent occurrence is, I believe, a result of trusting to Fehling’s solution as a test for peptones. That agent gives with other substances, certainly with albumen, a red colour which is not distinguishable from that which results from a peptonous mixture. Nothing can be easier than to separate peptones from albumen if they should be combined in the same urine. This may be done in two ways :-lst. The albumen having been coagulated by heat, the peptones, which are not affected by heat, may be separated by filtration. 2nd. The mixed peptones and albumen having been precipitated by picric acid, the peptones are redissolved by boiling, and then separated by pouring the boiling liquid on a previously heated filter. The coagulated albumen will be left on the filter, while the picrate of peptones in the filtrate will be reprecipitated on cooling. I claim, then, for picric acid that it is at once the most delicate and trustworthy known test for peptones in the urine. 2. It has been truly stated that picric acid gives with the vegetable alkaloids, such as those of cinchona, a precipitate like albumen-like it, that is, at first sight, but unlike it in being completely redissolved below the boiling-point of water, and therefore not to be mistaken for albumen by those who follow the rule of applying heat to every precipitate or opalescence caused by picric acid. It is only when ,

use

1084

large doses of the vegetable alkaloids are introduced into dose of quinine, that the stomach, such as a enough escapes through the kidneysto give a precipitate with picric acid. Cases may occur, such as those of poisoning by opium or its alkaloid, in which picric acid as a urinary test tor morphia might be of practical value. 3. It is a fact that picric acid, like nitric or any other acid, when added to urine, sometimes, though rarely, causes a turbidity from precipitated urates; this precipitate, however, unlike albumen, is at once and completely redissolved by heat. 4. It has been repeatedly and confidently asserted that picric acid precipitates mucin, but this statement can easily be proved to be erroneous. In fact, picric acid is the only

five-grain

albumen, except heat, which has no apparent All normal urines contain, partly in solution, and therefore not separable by filtration, and partly suspended, a substance which it is the custom to call mucin, common test for effect on mucin.

and which is known to be coagulable by acetic and citric and by the dilute mineral acids. A few drops of a cetic or solution of citric acid added to most, if not all, normal urines render

them, in the course of a minute or two, slightly but decidedly hazy or opalescent when viewed against a dark background, which is essential in all cases of delicate testing. This haziness forms slowly, and is in no degree increased or diminished by boiling. So with nitric acid, as Dr. Wm. Roberts correctly and clearly states in the recently published lY!edical Chronicle, p. 2, "when a urine, containing both albumen and mucin is tested by the contact method with nitric acid, the albumen is thrown down just above the line of junction of the two fluids, while the mucin is brought into view towards the upper part of the column of urine, where it gradually forms a diffused haze, quite distinct from the opalescent zone at the line of junction." This haze is due to the action of the nitric acid, diluted by diffusion through the urine, upon the mucin. Now, when a saturated solution of picric acid is added in about an equal volume to a normal urine, the mixture remains quite transparent, except in the rare case of turbidity resulting from precipitated urates, which heat would at once remove. But the addition of acetic or citric acid to the mixture of picric acid and urine will gradually cause a considerable haziness, as will the addition of picric acid solution to urine with which acetic acid has been previously mixed. In this experiment the picric acid renders more apparent the haziness which results, not from the picric, but from the action of the acetic or citric acid. In short, picric acid alone has no visible effect upon mucin, while picric acid with acetic or citric acid causes a mucin haziness in most, if not all, normal urines. One of the most conclusive proofs that picric acid does not coagulate mucin is afforded by the fol. lowing experiment :-Add to an albuminous urine of normal acidity an equal volume of picric acid solution, then boil so as to ensure the complete coagulation of the albumen, and filter. Add a few drops of acetic or citric acid solution to the clear filtrate, and the result will be, in a minute or two, the appearance of a slight, but perceptible, haze of mucin which the combined influence of picric acid and heat had left in the solution, and so passable through the filter. It is obvious from the foregoing statement of indis-

facts that any test for albumen which requires its action the combination or the addition of acetic or citric acid is liable to the fallacy that it will give with the mucin present in normal urine an opalescence or haziness which is not distinguishable from that caused by a minute trace of albumen. This remark applies to the tungstate of soda, the ferro-cyanide of potassium, and the potassio-mercuric iodide, but especially to the last-mentioned test. The potassio-mercuric iodide, which, without the addition of acetic or citric acid, gives no reaction with albumen, with that addition causes in most, if not all, normal urines a decided mucin opalescence. I say in most normal urines, because although I have found this result in all the normal urines which I have examined, it is possible that there may be some exceptions. It is manifest therefore that picric acid, which requires the addition of no other acid, has a decided advantage over those tests which do require such an addition. It is true that picric acid will not coagulate albumen in an alkaline urine, but an excess of the test is sufficient to acidify most alkaline urines. If, however, a be highly alkaline and ammoniacal, the safest method of procedure is to acidify with acetic or citric acid, then to picric acid to the filtrate. The mucin filter and add the acetic or citric acid will remain on coagulated by

putable

for

specimen

the filter, while the albumen, if present, will pass through. Here, be it observed, the mucin of normal urine must not be confounded with the morbid mucus from an inflamed or catarrhal mucous membrane. The mucus which is secreted by an inflamed bladder or urethra or vagina is allied both chemically and microscopically to pus, and, like pus, contains albumen. The presence of morbid mucus in the urine renders the secretion visibly turbid, and the turbidity must be removed by filtration before the tests for albumen can be conveniently applied. Obviously in practice it is of primary importance to distinguish uterine or vaginal, vesical or urethral sources of muco-purulent albuminuria from that which is of renal origin, but it is no part of my present purpose to indicate the means by which this diagnosis is to be made. The result then of the various experiments with picric acid has been to show that albumen is the only materialfouncl in the urine which gives with picric acid an opalescence or a precipitate which is insoluble by heat. The most delicate test for a minute trace of albumen is to allow the picric acid solution to mix, and not merely to come in contact, with about two inches of the upper part of a long column of urine in a test tube, and then to boil the top of the liquid. The more or less turbid upper layer contrasts with the clear urine below. The slight haziness caused by a mere trace of albumen is always increased by heat, whilethe turbidity caused by urates, &c., is completely removed by heat. If the urine before testing is rendered turbid by urates these must be removed by heat before the picric acid is added, and if by mucus or other floating particles the fluid must be cleared by filtration. When the albumen is very copious the coagulum formed by a few drops of picric acid solution is redissolved, and an excess of the test is required to produce a permanent precipitate. It is manifest, therefore, that the mere contact of a column of picric acid solution, without mixture with such a specimen, might give no indication of of albumen. A similar source of error exists in the presence " using the so-calledII contact method with nitric acid. I once saw a clinical clerk so carefully pour a column of urine on nitric acid, previously placed in a test-tube, that the two liquids came into contact without mixing. The result was a slight opacity at the junction of the two liquids, and the inference that a mere trace of albumen was present ; but as the history of the case had led me to expect an abundance of albumen, I gave the test-tube a shake, when the mixed liquids became nearly solid with albumen. It is a well-known fact t*iat while an excess of nitric acid redissolves coagulated albumen, especially when the mixture is heated, an excess of picric acid has no such misleading effect. 5. It can scarcely be urged as an objection to picric acid as a test for albumen, that to avoid some sources of fallacy the simultaneous or subsequent application of heat is’ necessary. There is no known single test which, by itself, can be relied upon. This remark is especially applicable to the nitric acid and the boiling tests, each of which employed alone has been, and must continue to be, a source of error. Picric acid as a qualitative and quantitative test J01’ sugar.-Although my proposal to employ picric acid with potash as a qualitative and quantitative test for sugar in the urine gave rise to a prolonged and somewhat acrimonious controversy, the result of the discussion may be very briefly summarised. It was admitted that when a solution of grape sugar is boiled with picric acid and potash, the yellow picric acid is partially deoxidised and converted into the red coloured picramic acid. This reaction had been observed by Braun, a German chemist, about twenty years ago, but it had never been practically utilised until, " by a happy accident," I rediscovered it.! It was also known to chemists that the alkaline sulphides have the same reducing effect as glucose on picric acid, and it was therefore contended that the unoxidised sulphur com. pounds in urine, and especially in albuminous urine, would form an alkaline sulphide when boiled with caustic potash, and so prove a source of fallacy. I soon found that the practical results were not in accordance with the theoretical objections ; for in analysing by the picric acid process a highly albuminous urine, which was also saccharine, one specimen before and another after the removal of the albumen by heat, the results were so nearly identical that for clinical purposes it was not worth while to remove the albumen. And when, before analysing the urine, it was filtered through animal charcoal, so as to remove some colouring matter which appears to be associated with the 1

See THE

LANCET, Nov. 18th,

1882.

1085 albumen, the results of the analysis of the albuminous and bowels, and great inconvenience was experienced. Retenthe dealbuminised urine by the picric acid process were tion of fluid fsecal matter could only be effected by sitting

found to be perfectly identical. Ultimately my son succeeded in proving to demonstration that the formation of an alkaline sulphide by boiling unoxidised sulphur compounds with potash depends upon the strength of the alkaline solu-

tion. When albuminous liquids or other sulphur compounds are boiled with a strong solution of caustic potash an alkaline sulphide is formed. On the contrary, when unoxidised sulphur compounds are boiled with such weak solutions as are employed in testing and analysing saccharine urine no alkaline sulphides are formed, and the picric acid process of quantitative sugar analysis is liable to no such fallacy as theoretical considerations had suggested.2 The ready method of qualitative albumen and sugar testing consists in adding to about a drachm of urine in a test tube an equal volume of picric acid solution. This, when boiled in accordance with the rules before given, affords a certain indieation of the presence or absence of albumen ; then, whether albumen be present or not, add about half a drachm of liquor potassae (P.B.), and boil for about half a minute. Any coagulated albumen that may be present is redissolved by the alkali, and the resulting colour in a non-saccharine urine is claret red. A good practical rule is that if any red colour is visible through the boiled column of liquid in the test tube, there is less than two grains of sugar per ounce. A solution of glucose in the proportion of two grains to the ounce, after boiling for a few seconds with picric acid and potash, .appears quite black until it is diluted with water. Then, having ascertained the presence of sugar, we proceed to make a uantitative analysis by means of the "picro-saccharometer."3 I have good reason for my belief that practitioners not much accustomed to testing for sugar will find the picric acid method much easier than the copper process. A very common source of error is this, that the slightly coloured phosphatic sediment thrown down by the alkali in the copper solution is mistaken for suboxide of copper, and sugar is erroneously supposed to be present when the urine is perfectly normal. The materials for bedside albumen and sugar testing may be conveniently and safely carried in a solid form in a pocket test-case, the picric acid in powder and the potash in grain lumps. These, with a small spirit lamp, are all packed into a waistcoat-pocket case by Mr. Hawksley, 357, ,Oxford-street; or they may be carried in Jahncke’s larger, but very pretty, cheap, and convenient case, which was favourably noticed in THE LANCET of September 20th, 1884. One of the main objects of this communication has been to promote and facilitate the practice of testing the urine in every case of disease, however trivial it may appear. When this practice becomes general, as it ought to be, there will be fewer cases of disease of the kidney passing on to the stage of hopeless and incurable

legs tightly crossed. In 1882 she was sent to school at Brighton.*While there the relaxation ceased, and although faeces and flatus passed through both openings sheexperienced little inconvenience. In 1883 the patient began to suffer violent abdominal pains, which induced her mother to relate the whole case to a medical friend, who advised that Mr. with the

Jonathan Hutchinson should be consulted. He saw her, and gave a rather unfavourable prognosis, but recommended the mother to let me see the case, and obtain my opinion as to whether any operation would be feasible and likely to succeed. In February, 1884, the patient was brought to me. She was seventeen years of age and in good health. The catamenia had appeared when twelve years old. A lodgment of hard faecal matter in the colon had been discovered recently, and to a great extent removed by suitable treatment. On examination I found the malformation, previous to any operation, to have been as depicted in Fig. 1. FIG. 1.

A, Bladder. B, Vagina. c, Rectum. D, Vulvar anus. E, Vulva.

It is well known that in early fcotal life the anal orifice is terminating in the uro-genital sinus, and that this condition of parts continues until the perineum descends and divides the rectum from the vagina. If this develop. mental action be arrested, what has been called atresia ani vaginalis results. This appellation, at no time very correct, is quite unsuitable in the present case, for the anal orifice was not found terminating in the vagina, but in the vulva, where the fossa navicularis is usually situated. The con. dition of parts as I discovered them is represented in Fig. 2. to be found

FM. 2.

degeneration before they are discovered. Savile-row, W.

________________

A CASE OF

CONGENITAL VULVAR ANUS CURED BY OPERATION. BY JAMES H. AVELING, M.D., SENIOR PHYSICIAN TO THE CHELSEA HOSPITAL FOR WOMEN.

THE subject of this rare malformation was born in 1866, and it was not until she was five weeks old that the unusual situation of the anal orifice was discovered. She was then taken to Sir Prescott Hewett, who made an opening into the rectum in the normal position of the anus. This was kept open by passing bougies more or less frequently for two years. Caustic was applied to the vulvar anus with the intention of causing it to close, but without effect. Up to the age of fifteen the patient was little troubled by the involuntary escape of faeces, constipation being habitual with her, and no motion passing without the use ofaperients. At this time a change of residence caused constant relaxation of the 2

The paper in which my son, G.

Stillingfleet Johnson, described his on Albumen was published in

observations On the Action of Potash the Chemical News, Feb. 23rd, 1883. 3 For the details of this easy,

the reader to my pamphlet

by Messrs. Smith, Elder, & columns of THE LANCET.

and accurate process I must refer Albumen and Sugar Testing, published Co., as may be seen in the advertising

on

rapid,

A, Vulvar

anus.

B, Artificial

anus.

The vulvar anus readily admitted the tip of the index-finger. Had coitus taken place while this condition of parts existed, the penis would most probably have penetrated the rectum instead of the vagina. The artificial anus was rigid and unyielding all round its margin, and could not be dilated so as to permit of any operative measures being performed through it. Faeces and flatus passed through both openings. Beyond this the patient had no except a feeling of want of support in the perineal region, " tumbling to pieces" when standing or walking. Strange to say, up to within a few months of seeing me she had been ignorant of her malformation, and thought her uncomfortable state was shared by all her sex. In February I endeavoured to close the

inconvenience,