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PANCREATIC SECRETION IN THE TREATMENT OF DIABETES.
607 with strong ’"past experience skin over the
antiseptics in wounds-my owll’ is prepared the night befor,e joint view. and again on the table witl1 usual in the manner, ;operation ,corrosive lotion once previous to operation. tourniquet of broad strong indiarubbe r 6
obtain the after-history of every case operated upon from 1900 to the end of 1907, not including. the last year as these are too recent to form a judgment upon. Of 58 cases done, 17 cannot be traced ; of the 41 returns, 3 cannot work and 38 report themselves able to work. The three cases that are unable to work have been seen and all had extensive osteo-arthritis in the knee-joint, two having had it well marked previous to the operation. All 38 successful cases were written to and 30’of these
of this. The knee is flexed and an incision made, a!s in Fig. 7, through the skin only. The knife with which thi;s incision was made is now rejected as unfit for furthe:r replied. Patients sent out with Splints. use and with a clean knife an incision is made through thl3 J. S., aged 58 yearsB began work 4 weeks after operation. extensor aponeurosis from the upper part of the skin incisior1 W. H., 35 16 . straight over the head of the tibia. In simple straight A. B., 16 forward cases this incision suffices ; in more difficult ones the 22 G. C., 10 incision is curved backwards over the inner part of the head. 41 J. N., 5 30 of the tibia, but must never divide the ligamentous struc W. C., 14 37 tures2 on the inner side of the joint beyond the skinI 10 G. H., 46 " incision. A free division of the ligaments here frequently J. M., 17 44 results in a joint capable of some lateral movement, and Patients sent out without Splints. consequently of a limb incapacitated for any sort of work, a W. C., aged 35 years, began work 24 weeks after operation. fact which has only been impressed upon me since I have to examine many miners for the compensation authoriA. T., 28 31 39 7 J. M., ties. On dividing the strong extensor aponeurosis a thick G. T., 12 68 pad of tough fat is exposed. This can be drawn forwards G. W., 20 39 between two clip forceps and divided in the line of the 13 W. C., 40 incision until the is at some As joint previous opened depth. J. MeC., 25 7 soon as air gains admission to the synovial cavity the incision B. C., 11 " 51 -can be readily extended to the whole length of the preceding 6 M. S., " 27 .one. With suitable retractors the joint cavity can now be J. P.. 11 52 examined, and a blunt hook under the free edge of the 13 J. C., , 32 ,cartilage shows whether it is unduly loose and aids the 14 G. P., 46 If the incision is found to be too small it is .search. H. H., 5 20 >, extended backwards along the head of the tibia in the joint. J. M., 39 12 J. D., 30 ,Through this incision the joint can be fully explored during 12 " 38 I first full flexion and then full extension, and if no lesion of the 24 W.O., W. S., 36 4, !cartilage is discovered further search must be made for the M. P., 16 22 ,cause of offence. If the cartilage is at fault the crack in it will , 35 7 ’" NY. R., already have been discovered and the cartilage is to be reJ. P., 6 39 moved. My general plan is to divide its anterior attachment , 16 R. A., 28 " ,; . ..first; then, holding this in clip -forceps, separate it by R. G., 39 20 .cutting the coronary attachment ’back beyond the middle its remove the ,line ; then, dividing cartilage transversely, The ’ average time before work was commenced by the ..anterior two-thirds. More than this is not necessary and who wore splints is 11 weeks. Those who wore no patients ,adds to the difficulties and dangers of the operation. After splints averaged 12-4- weeks. removal of the cartilage the wound is closed first by a conIn connexion with osteo-arthritis it was noted at the operatinuous suture of catgut through the extensor aponeurosis, tion of several cases that there were thickened hyperaemic ,then by a continuous catgut suture fortified by a few synovial membrane, synovial fringes, and some erosion of the silkworm-gut sutures through the skin. Separate cartilages covering the femur or tibia or both. In three of closure of the synovial membrane is ’unnecessary. In a these the disease was arrested by the operation, and,’ the single case, that of a youth with displaced external semi- movements of the joints are perfect. In no. single case that ,lunar cartilage, on whom I had operated, a small hernia on we can find was the joint made worse, and no patient was the outer side of the joint followed the operation. He had seriously ill after the operation. used the joint as soon as the wound healed and this may For the notes and records of these cases. I amindebted to with the but so had to do it troubled him little result, late house surgeon, Dr. Hamilton Drummond. my :that he was unaware of its presence till I pointed it out. Newcastle-on-Tyne. The wound is dressed with gauze wrung out of 1 in 1000 icorrosive spirit lotion, abundant cotton-wool, and a, firm bandage. When the dressing is completed, but not till PANCREATIC SECRETION IN THE then, the tourniquet is removed whilst the limb is elevated TREATMENT OF DIABETES. ,and kept so for a few minutes. Latterly I have discarded all splints and allowed the patient to put the limb in any BY W. M. CROFTON, M.B., B.CH. R.U.I. position he chose. Earlier I kept the knee entirely at rest in .efficient splints for an average of three weeks after operation. BEFORE describing the case and the treatment adopted I Now one dressing remains on for three weeks instead. It , was somewhat of a surprise to me to find in response to our will briefly consider the premises upon which the latter was that the splinted cases were rather better than those founded, recapitulating well-known facts so as to make what treated without splints. The numbers are, of course, too few follows the clearer. The Physiology of the carbohydrates, 4-c.-The ’saliva (given below) and the figures too close to draw any conclu,sion from and consideration of the fact that individuality, converts boiled starch and cane sugar into maltose and and perhaps compensation in many cases, prolongs the dextrin. A small amount of inversion also takes place in period of abstinence from work after operation has to be the stomach. The amylolytic ferment of the pancreas, amylopsin, is the chief agent in this inversion. The maltose taken into account. : After progress,-For a varying time after operation the and dextrin are then converted into dextrose by a ferment in joint remains weak and occasionally painful when worked, the intestinal juice, the cells lining the intestine have the but these symptoms gradually disappear, and after the first same power, and there is also a ferment with a similar year it is the rule for patients to say that the knee is as good function in the blood and tissue juices. The dextrose which ,as ever it was, and the cases we have inspected, numbering is absorbed by the intestinal mucosa is passed into the portal 20 unselected, bear this out fully. We have endeavoured to vein which conveys it to the liver cells ; these store up a certain amount of it, converting it into glycogen, while the 2 I purposely avoid saying internal lateral ligament, for this artificial rest passes on to supply the carbohydrate needs of the structure depends on the skilled dissection of the anatomist. All the aponeurotic structures are so welded with the ligaments as to be in- various tissues ; these also have in a more or less degree separable. power of converting dextrose into glycogen, forming local "
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608 The pancreas has been found to be stores. It appears that the fate of the liver glycogen of the pancreas. may be twofold : (a) when there is an extra demand for diseased in a large number of cases-e.g., intralobular and potential energy during a fasting period this glycogen is re- interacinar fibrosis and degeneration of the cells of the islets converted into dextrose and is burnt up in the conversion of of Langerhans. In treating a case of diabetes our first desire potential into kinetic energy, for instance, in the muscles ; must therefore be to remove the cause of the disability of the while (b) if there is no demand in the intervals between pancreas. If it be due to the deficient acidity of the gastric meals some of the glycogen is converted into fat. The juice leading to deficient conversion of prosecretin into liver cells have the glycogen-forming power in a super- secretin administer acids. (It is possible that some of the lative degree, the liver forming the great carbohydrate cases of transient glycosuria may be due to this cause.) If it be due to absence of prosecretin give secretin. Some cases reserve store, doling out more or less dextrose according to the needs of the tissues and in such quantities that normally of diabetes have been cured by this means. This is interestthere is not more than 0 - 2 per cent. in the blood. ing as it shows that the internal secretion is, like the external The glycogen formed in the liver and tissue cells may also be secretions, dependent for its production on this substance. The causes of the lesion in the pancreas itself are obscure built up by them from certain of the products of protein metabolism-e.g., alanine and aspartic acid, these being and there are probably several. I believe that, as Sir A. E. probably first converted into lactic acid from which glycogen Wright suggests, the pancreatic lesion may be due in some cases to an acute or subacute microbial inflammation which is elaborated. In breaking down the dextrose the tissue cells probably may subside and leave behind a greater or less degree of first convert it into lactic acid (this is known to take place in fibrosis. In order to treat this the ideal means would be a the liver) ; this is then further oxidised into water and C02. specific serum for the acute cases or a vaccine for the more In the absence of the pancreas the cells are incapable of chronic ones. Since this is impossible, owing to our ignorance I performing this reduction ; even a small piece of the pancreas of the causative microbe, perhaps the intravenous or intrapreserves this capacity to them. Fat may also be converted muscular injection of some powerful bactericide, such as a into carbohydrate, especially in the liver, but the precise! solution of iodoform in ether, might prove useful. Many cases way in which this change is effected is not properly known. of diabetes have followed acute inflammation of the gland The pancreas is induced to secrete by a substance termedl from different causes-e.g., it may be due to bile getting secretin, which is carried to it by the blood stream ; it is! into the pancreatic duct or the diabetes may be due to a slow. formed in the mucous membrane of the duodenum and upperr fibrosis spreading from the intralobular and interacinar part of the small intestine from a precursor called pro-- tissues, due to a chronic inflammation following blocking of secretin under the influence of the acid gastric contentss the pancreatic duct by a stone. Or the diabetes may be due when they enter this part of the intestine. to the poisoning of the pancreatic cells by a toxin produced Pathology.-The blood normally contains up to 0 -2 perr in other parts of the body-e.g., the removal of a gangrenous cent. of dextrose. If this percentage rises higher thee limb has led to the disappearance or a great improvement kidney cells remove it and it is excreted in the urine. Thiss in the amount of sugar. may happen as follows : (a) If owing to a very large intakee Since it is difficult with our present knowledge to remove of carbohydrate the liver and tissue cells have more than n the cause of the pancreatic lesion, the next best thing is to n they want for their immediate needs and more than they can replace the secretion and so to tide over an acute lesion till store up in the form of glycogen; the kidneys remove the the pancreas has more or less recovered its function, or in superfluous dextrose. (b) If the liver and tissue cells,s, the permanent sclerotic cases permanently to replace it, just especially the liver cells, are not in good form as regardsis as thyroid extract is given in cases where there is loss of re their glycogen-storing functions the same reserve store function in the thyroid. This apparently has never, as far nt as I can learn from a perusal of the literature, been successcannot be formed and so the temporarily superfluous amoun1 ’sof dextrose is removed as before. These two forms of glycos ful, probably because the pancreatic extract has been given t. by the mouth without anything to protect it from the hydronria can be successfully treated by limitation of diet tie chloric acid of the stomach, so that it has been destroyed (c) Glycosuria may be caused by lesions in the region of thl he there, and has thus been necessarily ineffective, or the medulla similar to glycosuria caused by puncture of th us floor of the fourth ventricle between the auditory and vagu extracts used may have been deficient in internal secretion. er nuclei. Puncture glycosuria only lasts as long as the live In the following case an extract containing all the pancreatic en contains glycogen and does not occur if the vagi have bee products (it being impossible to give the internal secretion previously cut. (d) The administration of certain drug;2:s, by itself as it has not been isolated) has been given in e.g., phloridzin or phloretin, causes glycosuria. These a( capsules insoluble in the stomach and when the acute )se through the kidney cells reducing the percentage of dextros symptoms subsided secretin has been given to try to in the blood ; the liver depletes itself of glycogen to repla( stimulate the damaged pancreas to do better work. the loss and when all the reserve store of carbohydrates is History and condition on examination.-The patient, a girl, his aged 13 years, was brought to me by her mother on Jan. 10th, used up, the sugar is formed from protein material. In th ria 1908, who informed me that for about three months she had last respect the phloridzin glycosuria resembles the glycosur which occurs in severe diabetes. Adrenalin also causses noticed that the child had a ravenous appetite and was tl glycosuria. (e) As mentioned above, in the absence of the passing large quantities of urine, so much so that the child ( at night to such an extent that was soaking her bed .e., pancreas the tissue cells are incapable of making use of-i. oxidising-the dextrose supplied to them (although the Ley, the water dripped down on the floor and came through e.g., the liver cells, may be still capable of forms ing to the ceiling of the room below. The patient had also t been complaining of headache and of a pain in the epiglycogen) ; this leads to an increase of the dextrose in the blood and so to glycosuria. This form of glycosuriais gastrium, and the mother had noticed that the child was identical with the glycosuria of severe diabetes and is acco: omvery blue and drowsy and that she had no energy. The panied by an increased nitrogenous metabolism, the tiss patient looked emaciated, drowsy, and somewhat eyanosed, cells in their craving for dextrose manufacturing it fr( rom and complained of headache and the epigastric pain, &c., as protein, and it appears that the dextrose so manufactuiired described above. The urine gave a well-marked dextrose can be made more use of by the cells of the diabetic th han reaction. I kept her under observation for a day or two that made from carbohydrates ; and further, that made frl rom without treatment and found that she was passing 12 pints the products of their own metabolism is more to their liki ,ting of urine that could be collected, besides soaking her bed to than that made from the products of foreign protein int the before-mentioned extent; 15 pints in the 24 hours must duced into the alimentary canal. be a low estimate of the total amount. This contained 10’5 From the above considerations it appears most proba able per cent. of dextrose and had a specific gravity of 1027. that severe glycosuria-that is, glycosuria produced fr ’rom There was no albumin and none of the ketones were present. both carbohydrates and proteins-is in some way or ot !ther The patient’s weight was 4 stones 6 pounds. The fermented due to failure in the pancreatic functions possibly ofE an urine gave Cammidge’s reaction A. Treatment was begun on Jan. 12th, when four capsules internal secretion. This failure may come about in seVE mi light containing the pancreatic product (Fairchild’s holadin) were ways. (a) The chyme entering the duodenum, &c., not be acid enough to change the prosecretin into secreetin. given. No alteration whatever was made in the diet. The effect was remarkable ; the amount of urine began to de(b) It may be due to the absence of secretin from the inntestinal mucosa. (o) It may be due to the loss of functioi of crease daily. On the 14th the amount of urine for the sease the internal secretion-that is, to disE the cells previous 24 hours was 10 pints and the patient had not
reserve
,
producing
609 wetted her bed nearly so much and she was brighter. On the 16th the urine was nine pints in amount and the bed was not wet at all. Dextrose, 10’2 per cent. On the 20th the amount of urine had fallen to eight pints with 11 per cent. dextrose, and the patient weighed 4 stones 12 pounds. On the 23rd the amount of urine had fallen to six pints with 10 per cent. dextrose. On the 27th the patient was given eight capsules in the day instead of four; this slightly increased the quantity of urine passed but not the percentage of sugar, this varying between 10 and 12 per cent. and her weight being maintained at about 4 stones 12 pounds, so that on the 31st the four capsules as originally given were resumed. On Feb. 12th, 13th, and 14th the amount of urine The patient did not wet the bed and was 4 pints. she was much brighter and her thirst and hunger were much less. On the 16th she had a slight relapse, the amount of urine rising to 10½ pints on the 17th. This was accompanied by a sore throat, epigastric pain, headache, and drowsiness. On the 26th the amount of urine had again fallen to six pints and the patient’s weight was 4 stones 13 pounds. From the 29th to March 10th no capsules were given and the weight of the patient on the latter date was 4 stones 12 pounds, the amount of urine being 6 pints with 11 per cent. of sugar. As the amount of urine then began to rise the patient was put on to the original number of capsules. The case and the treatment pursued much the same course, the capsules being intermitted now and then for a week or ten days until August 6th. On that day she passed 5 pints of urine containing 10 per cent. of sugar, and she weighed 4 stones 12 pounds. Thinking that the pancreas had probably then recovered sufficiently to stand an additional stimulus I administered a one-grain tablet of secretin three times a day after food instead of the capsules. This effected a reduction of both the percentage of sugar and the quantity of urine; on the 25th the former was 5-5 per cent., the latter three pints, and the patient’s weight was 4 stones 13 pounds. On the 27th, much to my disappointment, the patient relapsed with a sore throat and epigastric pain ; the secretin was stopped and she was put back on the pancreatic extract. The urine increased daily till on Sept. 22nd it reached its maximum amount of 12 pints. It was remarkable that after the first few days of her relapse, when her weight fell 3 pounds to 4 stones 10 pounds, there was no further loss of weight, indeed there was a slight increase, it being 4 stones 10½ pounds on Sept. 22nd. From that date the urine gradually decreased in amount until on the 29th it was three pints and contained 11 per cent. of dextrose, the patient’s weight being 4 stones 11 pounds. The capsules were then stopped and the secretin was resumed for ten days. The urine on Oct. 6th was three and a half pints and the child weighed 4 stones 12½ pounds, she had no abnormal thirst or appetite and she felt quite strong. On Nov. 9th the child still weighed 4 stones 12 pounds and the amount of urine was normal-namely, two and a half pints-and it contained 6’2 per cent. of sugar. She had then had no treatment for weeks. On the 10th I again started her on secretin in the hope of still further reducing the percentage of sugar. The amount of urine remained from two and a half to three pints daily with 5 per cent. of sugar till Jan. llth, 1909, when there was a slight relapse accompanied by a sore throat as before. The patient was therefore put back on the capsules and she gained 3 pounds in weight during the relapse. She now (Feb. 22nd) weighs 5 stones 2 pounds and is in excellent form. The above case could not well have been a worse one even for a child, and it formed a very severe test for any treatment ; this was increased by the fact that, except for a few weeks when she was given a larger quantity of potatoes than bread, no alteration of diet was made, I told her to eat and drink anything she liked. The slight change in diet had no effect on the quantity of urine or the percentage of sugar. The relapses, accompanied as they were by sore throat and epigastric pain, were very suggestive of a microbial inflammation of the gland ; they also demonstrate the effect of the capsules in stopping loss of weight and maintaining the patient’s strength during the acute phase. Another interesting point, and one at present inexplicable to me, is the fact that although the amount of urine fell under the influence of the pancreatic extract the percentage of sugar remained the same although the patient was passing a far less total quantity ; and that the percentage fell when the pancreas
received the additional stimulus of the secretin. Whether or not the patient will entirely lose the sugar in her urine depends on whether the gland entirely recovers. I very much regret that I have missed getting a swab of the child’s throat during one of the relapses for microbial investigation. I hope if I have another case with similar symptoms to try to attack the supposed microbes in one of the ways suggested above. The embryological work of J. Beard has thrown some light on the change that takes place in the nutrition of the foetus when the pancreas becomes functional. In order properly to realise its influence it is necessary to inquire into the condition of the foetus as regards its nutrition before the pancreas becomes functional-that is, before the "critical period," that time when all the foetal organs are laid down and the Owing to the pancreas and placenta become functional. asymmetry of the nitrogen and carbon atoms isomeric compounds of them can be built up in two directions. These isomeric compounds act differently with regard to polarised light, turning it to the right or left as the case may be. After fertilisation the egg begins to divide, forming first of all the trophoblast or chorion which is the representative of the asexual generation and is called the phorozoon by J. Beard. From the first division, however, there is one cell which in succeeding divisions is different to the rest, this is destined to form later the germ cells and sexual generation-i.e., the foetus which-unfolds on and flourishes at the expense of the trophoblast or asexual generation. The isomeric compounds on which these two generations live are different: the asexual lives on levorotatory glucose, levo-glycogen, and dextro-proteid; the sexual lives on dextro sugar, dextroglycogen, and levo-proteid. The cells of the trophoblast by means of their intracellular ferments burrow into the uterine wall, breaking up the levo-proteids and dextro-glycogen and dextrose and building them up into the isomeric dextroproteid and levo-glycogen and levo-sugar. The sexual generation, on the other hand, also by means of intracellular ferments, takes these and builds them up into the levo-proteid and dextro-sugars. When the placenta and pancreas become functional there is a change in the mode of nutrition of the cells of the fœtus; instead of preparing their own food by means of their intracellular ferments they have their food prepared for them by the extracellular ferments of the pancreas ; their food is no longer the dextro-proteid and levo-sugars but levo-proteid and dextro-sugars. How the pancreas efrects this change is obscure. It cannot be due to its external secretions, for in diabetes these are generally sufficient; it must be due to some substance absorbed into the blood, that is, to an internal secretion of some kind. It is, therefore, easy to realise the profound change that takes place when the pancreas loses its function ; in the absence of the internal secretion the tissue cells again become dependent on their own intracellular ferments as they were in the pre-critical period when they lived on levo-sugars (this is a possible explanation of the observation that levulose is better borne by diabetics than dextrose), and thus the dextro-sugar with which they are supplied cannot be used, the percentage of dextrose in the blood rises, and it is excreted by the kidneys. It will be noticed that the trophoblast cells are bathed by the alkaline maternal tissue juices while the pre-critical foetal cells have to absorb their food from the acid juices of the trophoblast tissues. This may suggest an explanation of the acidosis of the diabetic. I have not speculated on the effect the loss of function of the pancreas may have on proteid metabolism ; it is probably profound. It is possible that its power of changing proteid metabolism may be affected when that of changing carbohydrate metabolism is not and vice versd, or they may both be affected together, which may explain the worst cases of diabetes. Sutton Bridge, Wisbech.
CLINICAL SOCIETY
OF
MANCHESTER.-A meeting
of the above society was held on Feb. 16th, Dr. J. J. Cox, Dr. C. Christopher the President, being in the chair. Heywood opened a discussion on Whooping-cough. In the course of his remarks he laid great stress on the value of fresh air in the treatment of this disease and expressed the opinion that but little reliance was to be placed on
drugs.
antiseptics in wounds-my owll’ is prepared the night befor,e joint view. and again on the table witl1 usual in the manner, ;operation ,corrosive lotion once previous to operation. tourniquet of broad strong indiarubbe r 6
obtain the after-history of every case operated upon from 1900 to the end of 1907, not including. the last year as these are too recent to form a judgment upon. Of 58 cases done, 17 cannot be traced ; of the 41 returns, 3 cannot work and 38 report themselves able to work. The three cases that are unable to work have been seen and all had extensive osteo-arthritis in the knee-joint, two having had it well marked previous to the operation. All 38 successful cases were written to and 30’of these
of this. The knee is flexed and an incision made, a!s in Fig. 7, through the skin only. The knife with which thi;s incision was made is now rejected as unfit for furthe:r replied. Patients sent out with Splints. use and with a clean knife an incision is made through thl3 J. S., aged 58 yearsB began work 4 weeks after operation. extensor aponeurosis from the upper part of the skin incisior1 W. H., 35 16 . straight over the head of the tibia. In simple straight A. B., 16 forward cases this incision suffices ; in more difficult ones the 22 G. C., 10 incision is curved backwards over the inner part of the head. 41 J. N., 5 30 of the tibia, but must never divide the ligamentous struc W. C., 14 37 tures2 on the inner side of the joint beyond the skinI 10 G. H., 46 " incision. A free division of the ligaments here frequently J. M., 17 44 results in a joint capable of some lateral movement, and Patients sent out without Splints. consequently of a limb incapacitated for any sort of work, a W. C., aged 35 years, began work 24 weeks after operation. fact which has only been impressed upon me since I have to examine many miners for the compensation authoriA. T., 28 31 39 7 J. M., ties. On dividing the strong extensor aponeurosis a thick G. T., 12 68 pad of tough fat is exposed. This can be drawn forwards G. W., 20 39 between two clip forceps and divided in the line of the 13 W. C., 40 incision until the is at some As joint previous opened depth. J. MeC., 25 7 soon as air gains admission to the synovial cavity the incision B. C., 11 " 51 -can be readily extended to the whole length of the preceding 6 M. S., " 27 .one. With suitable retractors the joint cavity can now be J. P.. 11 52 examined, and a blunt hook under the free edge of the 13 J. C., , 32 ,cartilage shows whether it is unduly loose and aids the 14 G. P., 46 If the incision is found to be too small it is .search. H. H., 5 20 >, extended backwards along the head of the tibia in the joint. J. M., 39 12 J. D., 30 ,Through this incision the joint can be fully explored during 12 " 38 I first full flexion and then full extension, and if no lesion of the 24 W.O., W. S., 36 4, !cartilage is discovered further search must be made for the M. P., 16 22 ,cause of offence. If the cartilage is at fault the crack in it will , 35 7 ’" NY. R., already have been discovered and the cartilage is to be reJ. P., 6 39 moved. My general plan is to divide its anterior attachment , 16 R. A., 28 " ,; . ..first; then, holding this in clip -forceps, separate it by R. G., 39 20 .cutting the coronary attachment ’back beyond the middle its remove the ,line ; then, dividing cartilage transversely, The ’ average time before work was commenced by the ..anterior two-thirds. More than this is not necessary and who wore splints is 11 weeks. Those who wore no patients ,adds to the difficulties and dangers of the operation. After splints averaged 12-4- weeks. removal of the cartilage the wound is closed first by a conIn connexion with osteo-arthritis it was noted at the operatinuous suture of catgut through the extensor aponeurosis, tion of several cases that there were thickened hyperaemic ,then by a continuous catgut suture fortified by a few synovial membrane, synovial fringes, and some erosion of the silkworm-gut sutures through the skin. Separate cartilages covering the femur or tibia or both. In three of closure of the synovial membrane is ’unnecessary. In a these the disease was arrested by the operation, and,’ the single case, that of a youth with displaced external semi- movements of the joints are perfect. In no. single case that ,lunar cartilage, on whom I had operated, a small hernia on we can find was the joint made worse, and no patient was the outer side of the joint followed the operation. He had seriously ill after the operation. used the joint as soon as the wound healed and this may For the notes and records of these cases. I amindebted to with the but so had to do it troubled him little result, late house surgeon, Dr. Hamilton Drummond. my :that he was unaware of its presence till I pointed it out. Newcastle-on-Tyne. The wound is dressed with gauze wrung out of 1 in 1000 icorrosive spirit lotion, abundant cotton-wool, and a, firm bandage. When the dressing is completed, but not till PANCREATIC SECRETION IN THE then, the tourniquet is removed whilst the limb is elevated TREATMENT OF DIABETES. ,and kept so for a few minutes. Latterly I have discarded all splints and allowed the patient to put the limb in any BY W. M. CROFTON, M.B., B.CH. R.U.I. position he chose. Earlier I kept the knee entirely at rest in .efficient splints for an average of three weeks after operation. BEFORE describing the case and the treatment adopted I Now one dressing remains on for three weeks instead. It , was somewhat of a surprise to me to find in response to our will briefly consider the premises upon which the latter was that the splinted cases were rather better than those founded, recapitulating well-known facts so as to make what treated without splints. The numbers are, of course, too few follows the clearer. The Physiology of the carbohydrates, 4-c.-The ’saliva (given below) and the figures too close to draw any conclu,sion from and consideration of the fact that individuality, converts boiled starch and cane sugar into maltose and and perhaps compensation in many cases, prolongs the dextrin. A small amount of inversion also takes place in period of abstinence from work after operation has to be the stomach. The amylolytic ferment of the pancreas, amylopsin, is the chief agent in this inversion. The maltose taken into account. : After progress,-For a varying time after operation the and dextrin are then converted into dextrose by a ferment in joint remains weak and occasionally painful when worked, the intestinal juice, the cells lining the intestine have the but these symptoms gradually disappear, and after the first same power, and there is also a ferment with a similar year it is the rule for patients to say that the knee is as good function in the blood and tissue juices. The dextrose which ,as ever it was, and the cases we have inspected, numbering is absorbed by the intestinal mucosa is passed into the portal 20 unselected, bear this out fully. We have endeavoured to vein which conveys it to the liver cells ; these store up a certain amount of it, converting it into glycogen, while the 2 I purposely avoid saying internal lateral ligament, for this artificial rest passes on to supply the carbohydrate needs of the structure depends on the skilled dissection of the anatomist. All the aponeurotic structures are so welded with the ligaments as to be in- various tissues ; these also have in a more or less degree separable. power of converting dextrose into glycogen, forming local "
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608 The pancreas has been found to be stores. It appears that the fate of the liver glycogen of the pancreas. may be twofold : (a) when there is an extra demand for diseased in a large number of cases-e.g., intralobular and potential energy during a fasting period this glycogen is re- interacinar fibrosis and degeneration of the cells of the islets converted into dextrose and is burnt up in the conversion of of Langerhans. In treating a case of diabetes our first desire potential into kinetic energy, for instance, in the muscles ; must therefore be to remove the cause of the disability of the while (b) if there is no demand in the intervals between pancreas. If it be due to the deficient acidity of the gastric meals some of the glycogen is converted into fat. The juice leading to deficient conversion of prosecretin into liver cells have the glycogen-forming power in a super- secretin administer acids. (It is possible that some of the lative degree, the liver forming the great carbohydrate cases of transient glycosuria may be due to this cause.) If it be due to absence of prosecretin give secretin. Some cases reserve store, doling out more or less dextrose according to the needs of the tissues and in such quantities that normally of diabetes have been cured by this means. This is interestthere is not more than 0 - 2 per cent. in the blood. ing as it shows that the internal secretion is, like the external The glycogen formed in the liver and tissue cells may also be secretions, dependent for its production on this substance. The causes of the lesion in the pancreas itself are obscure built up by them from certain of the products of protein metabolism-e.g., alanine and aspartic acid, these being and there are probably several. I believe that, as Sir A. E. probably first converted into lactic acid from which glycogen Wright suggests, the pancreatic lesion may be due in some cases to an acute or subacute microbial inflammation which is elaborated. In breaking down the dextrose the tissue cells probably may subside and leave behind a greater or less degree of first convert it into lactic acid (this is known to take place in fibrosis. In order to treat this the ideal means would be a the liver) ; this is then further oxidised into water and C02. specific serum for the acute cases or a vaccine for the more In the absence of the pancreas the cells are incapable of chronic ones. Since this is impossible, owing to our ignorance I performing this reduction ; even a small piece of the pancreas of the causative microbe, perhaps the intravenous or intrapreserves this capacity to them. Fat may also be converted muscular injection of some powerful bactericide, such as a into carbohydrate, especially in the liver, but the precise! solution of iodoform in ether, might prove useful. Many cases way in which this change is effected is not properly known. of diabetes have followed acute inflammation of the gland The pancreas is induced to secrete by a substance termedl from different causes-e.g., it may be due to bile getting secretin, which is carried to it by the blood stream ; it is! into the pancreatic duct or the diabetes may be due to a slow. formed in the mucous membrane of the duodenum and upperr fibrosis spreading from the intralobular and interacinar part of the small intestine from a precursor called pro-- tissues, due to a chronic inflammation following blocking of secretin under the influence of the acid gastric contentss the pancreatic duct by a stone. Or the diabetes may be due when they enter this part of the intestine. to the poisoning of the pancreatic cells by a toxin produced Pathology.-The blood normally contains up to 0 -2 perr in other parts of the body-e.g., the removal of a gangrenous cent. of dextrose. If this percentage rises higher thee limb has led to the disappearance or a great improvement kidney cells remove it and it is excreted in the urine. Thiss in the amount of sugar. may happen as follows : (a) If owing to a very large intakee Since it is difficult with our present knowledge to remove of carbohydrate the liver and tissue cells have more than n the cause of the pancreatic lesion, the next best thing is to n they want for their immediate needs and more than they can replace the secretion and so to tide over an acute lesion till store up in the form of glycogen; the kidneys remove the the pancreas has more or less recovered its function, or in superfluous dextrose. (b) If the liver and tissue cells,s, the permanent sclerotic cases permanently to replace it, just especially the liver cells, are not in good form as regardsis as thyroid extract is given in cases where there is loss of re their glycogen-storing functions the same reserve store function in the thyroid. This apparently has never, as far nt as I can learn from a perusal of the literature, been successcannot be formed and so the temporarily superfluous amoun1 ’sof dextrose is removed as before. These two forms of glycos ful, probably because the pancreatic extract has been given t. by the mouth without anything to protect it from the hydronria can be successfully treated by limitation of diet tie chloric acid of the stomach, so that it has been destroyed (c) Glycosuria may be caused by lesions in the region of thl he there, and has thus been necessarily ineffective, or the medulla similar to glycosuria caused by puncture of th us floor of the fourth ventricle between the auditory and vagu extracts used may have been deficient in internal secretion. er nuclei. Puncture glycosuria only lasts as long as the live In the following case an extract containing all the pancreatic en contains glycogen and does not occur if the vagi have bee products (it being impossible to give the internal secretion previously cut. (d) The administration of certain drug;2:s, by itself as it has not been isolated) has been given in e.g., phloridzin or phloretin, causes glycosuria. These a( capsules insoluble in the stomach and when the acute )se through the kidney cells reducing the percentage of dextros symptoms subsided secretin has been given to try to in the blood ; the liver depletes itself of glycogen to repla( stimulate the damaged pancreas to do better work. the loss and when all the reserve store of carbohydrates is History and condition on examination.-The patient, a girl, his aged 13 years, was brought to me by her mother on Jan. 10th, used up, the sugar is formed from protein material. In th ria 1908, who informed me that for about three months she had last respect the phloridzin glycosuria resembles the glycosur which occurs in severe diabetes. Adrenalin also causses noticed that the child had a ravenous appetite and was tl glycosuria. (e) As mentioned above, in the absence of the passing large quantities of urine, so much so that the child ( at night to such an extent that was soaking her bed .e., pancreas the tissue cells are incapable of making use of-i. oxidising-the dextrose supplied to them (although the Ley, the water dripped down on the floor and came through e.g., the liver cells, may be still capable of forms ing to the ceiling of the room below. The patient had also t been complaining of headache and of a pain in the epiglycogen) ; this leads to an increase of the dextrose in the blood and so to glycosuria. This form of glycosuriais gastrium, and the mother had noticed that the child was identical with the glycosuria of severe diabetes and is acco: omvery blue and drowsy and that she had no energy. The panied by an increased nitrogenous metabolism, the tiss patient looked emaciated, drowsy, and somewhat eyanosed, cells in their craving for dextrose manufacturing it fr( rom and complained of headache and the epigastric pain, &c., as protein, and it appears that the dextrose so manufactuiired described above. The urine gave a well-marked dextrose can be made more use of by the cells of the diabetic th han reaction. I kept her under observation for a day or two that made from carbohydrates ; and further, that made frl rom without treatment and found that she was passing 12 pints the products of their own metabolism is more to their liki ,ting of urine that could be collected, besides soaking her bed to than that made from the products of foreign protein int the before-mentioned extent; 15 pints in the 24 hours must duced into the alimentary canal. be a low estimate of the total amount. This contained 10’5 From the above considerations it appears most proba able per cent. of dextrose and had a specific gravity of 1027. that severe glycosuria-that is, glycosuria produced fr ’rom There was no albumin and none of the ketones were present. both carbohydrates and proteins-is in some way or ot !ther The patient’s weight was 4 stones 6 pounds. The fermented due to failure in the pancreatic functions possibly ofE an urine gave Cammidge’s reaction A. Treatment was begun on Jan. 12th, when four capsules internal secretion. This failure may come about in seVE mi light containing the pancreatic product (Fairchild’s holadin) were ways. (a) The chyme entering the duodenum, &c., not be acid enough to change the prosecretin into secreetin. given. No alteration whatever was made in the diet. The effect was remarkable ; the amount of urine began to de(b) It may be due to the absence of secretin from the inntestinal mucosa. (o) It may be due to the loss of functioi of crease daily. On the 14th the amount of urine for the sease the internal secretion-that is, to disE the cells previous 24 hours was 10 pints and the patient had not
reserve
,
producing
609 wetted her bed nearly so much and she was brighter. On the 16th the urine was nine pints in amount and the bed was not wet at all. Dextrose, 10’2 per cent. On the 20th the amount of urine had fallen to eight pints with 11 per cent. dextrose, and the patient weighed 4 stones 12 pounds. On the 23rd the amount of urine had fallen to six pints with 10 per cent. dextrose. On the 27th the patient was given eight capsules in the day instead of four; this slightly increased the quantity of urine passed but not the percentage of sugar, this varying between 10 and 12 per cent. and her weight being maintained at about 4 stones 12 pounds, so that on the 31st the four capsules as originally given were resumed. On Feb. 12th, 13th, and 14th the amount of urine The patient did not wet the bed and was 4 pints. she was much brighter and her thirst and hunger were much less. On the 16th she had a slight relapse, the amount of urine rising to 10½ pints on the 17th. This was accompanied by a sore throat, epigastric pain, headache, and drowsiness. On the 26th the amount of urine had again fallen to six pints and the patient’s weight was 4 stones 13 pounds. From the 29th to March 10th no capsules were given and the weight of the patient on the latter date was 4 stones 12 pounds, the amount of urine being 6 pints with 11 per cent. of sugar. As the amount of urine then began to rise the patient was put on to the original number of capsules. The case and the treatment pursued much the same course, the capsules being intermitted now and then for a week or ten days until August 6th. On that day she passed 5 pints of urine containing 10 per cent. of sugar, and she weighed 4 stones 12 pounds. Thinking that the pancreas had probably then recovered sufficiently to stand an additional stimulus I administered a one-grain tablet of secretin three times a day after food instead of the capsules. This effected a reduction of both the percentage of sugar and the quantity of urine; on the 25th the former was 5-5 per cent., the latter three pints, and the patient’s weight was 4 stones 13 pounds. On the 27th, much to my disappointment, the patient relapsed with a sore throat and epigastric pain ; the secretin was stopped and she was put back on the pancreatic extract. The urine increased daily till on Sept. 22nd it reached its maximum amount of 12 pints. It was remarkable that after the first few days of her relapse, when her weight fell 3 pounds to 4 stones 10 pounds, there was no further loss of weight, indeed there was a slight increase, it being 4 stones 10½ pounds on Sept. 22nd. From that date the urine gradually decreased in amount until on the 29th it was three pints and contained 11 per cent. of dextrose, the patient’s weight being 4 stones 11 pounds. The capsules were then stopped and the secretin was resumed for ten days. The urine on Oct. 6th was three and a half pints and the child weighed 4 stones 12½ pounds, she had no abnormal thirst or appetite and she felt quite strong. On Nov. 9th the child still weighed 4 stones 12 pounds and the amount of urine was normal-namely, two and a half pints-and it contained 6’2 per cent. of sugar. She had then had no treatment for weeks. On the 10th I again started her on secretin in the hope of still further reducing the percentage of sugar. The amount of urine remained from two and a half to three pints daily with 5 per cent. of sugar till Jan. llth, 1909, when there was a slight relapse accompanied by a sore throat as before. The patient was therefore put back on the capsules and she gained 3 pounds in weight during the relapse. She now (Feb. 22nd) weighs 5 stones 2 pounds and is in excellent form. The above case could not well have been a worse one even for a child, and it formed a very severe test for any treatment ; this was increased by the fact that, except for a few weeks when she was given a larger quantity of potatoes than bread, no alteration of diet was made, I told her to eat and drink anything she liked. The slight change in diet had no effect on the quantity of urine or the percentage of sugar. The relapses, accompanied as they were by sore throat and epigastric pain, were very suggestive of a microbial inflammation of the gland ; they also demonstrate the effect of the capsules in stopping loss of weight and maintaining the patient’s strength during the acute phase. Another interesting point, and one at present inexplicable to me, is the fact that although the amount of urine fell under the influence of the pancreatic extract the percentage of sugar remained the same although the patient was passing a far less total quantity ; and that the percentage fell when the pancreas
received the additional stimulus of the secretin. Whether or not the patient will entirely lose the sugar in her urine depends on whether the gland entirely recovers. I very much regret that I have missed getting a swab of the child’s throat during one of the relapses for microbial investigation. I hope if I have another case with similar symptoms to try to attack the supposed microbes in one of the ways suggested above. The embryological work of J. Beard has thrown some light on the change that takes place in the nutrition of the foetus when the pancreas becomes functional. In order properly to realise its influence it is necessary to inquire into the condition of the foetus as regards its nutrition before the pancreas becomes functional-that is, before the "critical period," that time when all the foetal organs are laid down and the Owing to the pancreas and placenta become functional. asymmetry of the nitrogen and carbon atoms isomeric compounds of them can be built up in two directions. These isomeric compounds act differently with regard to polarised light, turning it to the right or left as the case may be. After fertilisation the egg begins to divide, forming first of all the trophoblast or chorion which is the representative of the asexual generation and is called the phorozoon by J. Beard. From the first division, however, there is one cell which in succeeding divisions is different to the rest, this is destined to form later the germ cells and sexual generation-i.e., the foetus which-unfolds on and flourishes at the expense of the trophoblast or asexual generation. The isomeric compounds on which these two generations live are different: the asexual lives on levorotatory glucose, levo-glycogen, and dextro-proteid; the sexual lives on dextro sugar, dextroglycogen, and levo-proteid. The cells of the trophoblast by means of their intracellular ferments burrow into the uterine wall, breaking up the levo-proteids and dextro-glycogen and dextrose and building them up into the isomeric dextroproteid and levo-glycogen and levo-sugar. The sexual generation, on the other hand, also by means of intracellular ferments, takes these and builds them up into the levo-proteid and dextro-sugars. When the placenta and pancreas become functional there is a change in the mode of nutrition of the cells of the fœtus; instead of preparing their own food by means of their intracellular ferments they have their food prepared for them by the extracellular ferments of the pancreas ; their food is no longer the dextro-proteid and levo-sugars but levo-proteid and dextro-sugars. How the pancreas efrects this change is obscure. It cannot be due to its external secretions, for in diabetes these are generally sufficient; it must be due to some substance absorbed into the blood, that is, to an internal secretion of some kind. It is, therefore, easy to realise the profound change that takes place when the pancreas loses its function ; in the absence of the internal secretion the tissue cells again become dependent on their own intracellular ferments as they were in the pre-critical period when they lived on levo-sugars (this is a possible explanation of the observation that levulose is better borne by diabetics than dextrose), and thus the dextro-sugar with which they are supplied cannot be used, the percentage of dextrose in the blood rises, and it is excreted by the kidneys. It will be noticed that the trophoblast cells are bathed by the alkaline maternal tissue juices while the pre-critical foetal cells have to absorb their food from the acid juices of the trophoblast tissues. This may suggest an explanation of the acidosis of the diabetic. I have not speculated on the effect the loss of function of the pancreas may have on proteid metabolism ; it is probably profound. It is possible that its power of changing proteid metabolism may be affected when that of changing carbohydrate metabolism is not and vice versd, or they may both be affected together, which may explain the worst cases of diabetes. Sutton Bridge, Wisbech.
CLINICAL SOCIETY
OF
MANCHESTER.-A meeting
of the above society was held on Feb. 16th, Dr. J. J. Cox, Dr. C. Christopher the President, being in the chair. Heywood opened a discussion on Whooping-cough. In the course of his remarks he laid great stress on the value of fresh air in the treatment of this disease and expressed the opinion that but little reliance was to be placed on
drugs.