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were always higher and sometimes considerably higher in the morning on an empty stomach than in the evening, despite the fact that the patient took a not inconsiderable amount of food during the day. The greatest rise was from 0,168 to 0,248, - an increase of O,OS, and almost equivalent to the blood’s normal sugar content. The smallest rise was 0,023. An interposed fasting-- day was also followed by a decided paradoxical rise of 0,064. Leaving out of account the rise after fasting and the day on which a fall occurred, the mean of the 16 rises is 0,042. I must add that in this patient the phenomena were unusually well marked.

Time forbids my further discussing the influence of meals. The same periodicity in the concentration of the blood sugar

which I have discovered in a number of diabetic patients is also found in the excretion of sugar in the urine. The urine is collected a t intervals of 4 hours. The sugar excretion is greatest in the morning and falls toward the evening after which it rises again during the night in accordance with the simultaneous variations in the blood sugar.

This periodicity which has been demonstrated in a number of diabetics both while fasting and also while taking food, must be taken into consideration when judging the effect of meals or other external factors on the blood sugar.

H.F.Hest. Urine Sugar and its Relation to Blood Sugar.

Ever since WORM MULLER’S and NYLANDER’S investigations in the latter half of the last century we have known that the urine of healthy persons regularly contains sugar. The amount of this sugar is, as is known, so small that it has been impossible to estimate i t by the usual quantitative methods, nor have we succeeded in elucidating the nature of the sugar with certainty and especially is i t still undecided whether glucose is a physiolo- gical constituent of urine.

In 1918 BENEDICT and OSTERBERG described a method the principle of which was to determine the reduction in urine before and after fermentation. The difference between the power of re- duction in the fermented and unfermented urine is a measure

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of the reducing fermentable substances of the urine which may all be classed under the term w i n e sugar)). In the form described by BENEDICT and OSTERBERG the method is not reliable and I therefore modified it so that i t was applicable to the determination of urine sugar with a maximum error of 10 to 15 %. By this method and By HAGEDORN and NORMAN JENSEN’S method the urine sugar and its relation to the blood sugar was determined in about 50 healty persons and diabetics.

In 7 healthy men who were examined for 37 days on an ordinary diet the amount of urine sugar in the 24 hours’ sample varied between 180 and 710 mg., the aver- age being 368 mg. Diagram I shows the sugar excretion during a week in one of the persons investigated. As will be observed it varies rather much from day to day. Themini- mum in this case being about 300 mg.and the maximum about 500mg.

The excretion in every case was greater by day than by night and was least in the morning before breakfast.

The effect of a series of different foodstuffs was investigated in the morning, the urine sugar being determined in one hour’s urine just before the meal and in 2 or 3 hours’ samples after the meal, while the blood sugar was determined just before and every quarter of an hour for two or three hours after the meal.

Bread in quantities of 100-300 g. almost always produced increase in the urine sugar, and i t was more pronounced the coarser the bread was. The excretion was greatest with brown bread. The blood sugar concentration showed a rise after. a meal of bread, but, in contrast to the urine sugar, it was greatest after fine grade bread, less after coarse bread, and least after brown bread, and the maximum blood sugar concentration was always observed during the first hour after the meal, while the maximum urine sugar concentration occurred as a rule in the third hour. Diagram I1 is an example of this. As will be observed the urine sugar was 16 mg. and the urine sugar concentration 0,4 per mille in the hour before the experiment, while the blood sugar concentration

Diagram I.

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also before the meal was 95 nig. per 100 ~ m . ~ blood. In tlie firs1 hour after 100 g. brown bread was taken there was a trifling increase in the urine sugar and a little increase in the blood sugar.

In the second hour the urine sugar increased enormously, reaching 32 mg. while the concentration was increased a t the same time to 1,6 per mille, and the blood sugar decreased somewhat. In the third hour the urine sugar further increased, the concen- tration reaching 1,8 per mille, while the blood sugar fell to its original level. In the second and third hours BENEDICT’S reaction was positive but the phenylhydrazin reaction was negative.

In a few experiments meat, green stuff, and soup produced

a minute increase in the urine sugar, but in most cases it had no effect. The blood sugar was quite unchanged in these experiments.

Blood sugar rises followed the administration of glucose in quan- tities of 50-100 g. dissolved in 200 cm.3 water, which varied greatly and which had no influence on the urine sugar provided that the renal threshold was not exceeded, as will be seen from diagram I11 which shows the blood sugar rise to 216 mg. without the amount of urine sugar being changed. In 25 medical students and convalescents the si- tuation of the renal threshold va- ried betweenless than 114andmore than 216 mg. per 100 cm.3 blood.

Diagrani 11.

Diagram 111.

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On the simultaneous administration of 100 g. brown bread and 50 g. glucose, as diagram IV shows, there was marked hyperglycaemia in the first hour while the urine sugar was almost unchanged. In the 2nd and 3rd hours the blood sugar had fallen to normal, while the urine sugar particularly in the 3rd. hour showed a considerable increase. The hyperglycaemia in the same person was equally great whether 50 g. glucose was given alone or together with brown bread, just as the increase in the urine sugar after brown bread was not influenced by 50 g. glucose when the renal threshold was not transgressed. The work of digestion and absorption therefore does not affect the carbohydrate tolerance as measured by the blood sugar, nor the position of the renal threshold.

In clinically sugar-free diabetics the same amount of urine sugar was found in the 24 hours’urine sample as in healthy persons, and the excretion was independent of variations in the diet when the renal threshold was not exceeded. With the inception of clini- cally demonstrable glycosuria the urine sugar was suddenly in- creased to many times its value. This great increase, with attendant polyuria, was often demonstrable one or two days before the qualitative sugar reactions became positive and could also be detected a day or two after the clinical glycosuria ceased, after which the urine sugar suddenly sank to its previous level. Dia- gram V shows how the urine sugar is immediately increased to 5 times its concentration when the carbohydrates in the diet are augmented from 16 to 25 gm. As soon as the amount of carbo- hydrates is again diminished the urine sugar falls to its previous amount. A fresh increase in the amount of carbohydrates and calories again produces marked increase in the urine sugar while

Diagram IV.

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considerable decrease only reduces the urine sugar to the amount generally found in healthy persons.

Changes in the blood sugar concentration brought about by the administration of glucose did not affect the urine sugar in diabetics when the renal threshold was not passed. Diagram VI

Diagram V.

shows how the blood sugar rose to 170 mg. after 6 g. glucose, while the urine sugar was absolutely unchanged.

Meat in quantities of 300 g. seems to be able to depress the renal threshold in diabetics, as will be observed from diagrams VI, VII, and VIII, which represent experiments on the same patient. As appears from diagram VII a bloood sugar rise occurs after 300 g. meat which is less than in the preceding experiment, but which is accompanied by a decided increase in the urine sugar, and in experiment VIII where 50 gm. glucose are given one hour after 300 gm. meat the same blood sugar rise occurs as in experiment VI, but while in the latter there was no change in the urine sugar in experiment VIII there is a very considerable increase.

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As will be seen from these experiments the blood sugar and the urine sugar are largely independent of each other, as variations in the blood sugar, which do not exceed the renal threshold, do not influence the urine sugar, while increase in the urine sugar can be brought about without change in the blood sugar. We can therefore distinguish between two kinds of sugar excretion namely,

1. the physiological sugar excretion which is constantly present both in healthy persons and in diabetics and which is independent of the blood sugar, and

Diagraiii Vl . Diagram VII. Diagram VIII.

2. the pathological sugar excretion which is due to the excretion of the glucose in the blood when the renal threshold is passed.

Since the physiological urine sugar is not affected by variations in the glucose concentration of the blood, it is a priori not probable that the urine sugar is glucose. In order to find out if possible whether glucose is present in normal urine a series of experiments with the phenylhydrazin reaction were made which were carried out with pure phenylhydrazin roughly as described by NEUMANN. On examination of many normal urines the so-called physiological osazones were always found but typical glucoiazones were never observed although these were formed when from 0,14,2 per mille glucose was added to the urines.

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As the fermentable sugar of normal urine usually varies be- tween 0,2 and 0,5 per mille but frequently rises to 1 per mille and above without the phenylhydrazin reaction becoming positive while it is only necessary to add 0,1--0,2 per mille glucose to get a positive reaction, i t is evident that the major portion of the sugar occurring in normal urine cannot be glucose.

I t might however be thought that glucose constituted a part of the fermentable substances in normal urine, and that the con- centration of glucose was too low to give a positive phenylhydrazin reaction. The reaction was therefore carried out in a series of urines evaporated to and 'Ilo of their volume but with consistently negative results; numerous physiological osazones were formed but never typical glucosazones. Further investigations showed however that the increased concentration of the urines depressed the sensitiveness of the phenylhydrazin reaction so much that the existence of glucose in normal urine could not be excluded by a negative reaction. This was probable due to the increased concentration of urea and ammonium salts, as NEUBERG has shown, therefore a number of experiments were performed in which the nitrogenous constituents of the urine had been first removed, partly with PATEIN'S fluid and partly with blood charcoal and acetic acid as ANDERSEN has recommended, after which the filtrates were made weakly acid and evaporated to '/lo volume. In these evaporated filtrates the phenyhyldrazin reaction was also negative.

Lastly a series of experiments was made with fermented urines. In these no osazones were formed from which i t may be concluded that the physiological osazones are dependent on the presence of carbohydrates in the urine. When weighed quantities of glucose were added to the fermented urines the phenylhydrazin reaction became positive a t a glucose concentration which was only slightly greater than that required to make the reaction positive in the same urine,before fermentation. To a normal urine which for example contained 0,5 per mille urine sugar i t was necessary to add 0,l per mille glucose to produce glucosazones. After fermenta- tion of the 0,5 pek mille urine sugar only 0,2 per mille glucose was needed to produce typical glucosazones, - in other words, if the normal urine sugar was replaced with an equivalent amount

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of glucose or only a fraction of i t the phenylhydrazin reaction became positive.

These experiments do not exclude the possibility that minimal amounts of glucose may occur in normal urine but they prove that the major portion of the carbohydrates contained in the urine of healthy persons is not glucose.

The nature of the physiological urine sugar is not evident from these investigations but as it is found in the urine on complete starvation and since the excretion is augmented by food containing bran we can, as in the case of uric acid, distingdish between an endogenous and an exogenous portion.

I t is of practical importance that the physiological urine sugar in concentrated urine can attain so great a concentration that the ordinary reduction reactions are positive. In order to decide in such cases whether glycosuria or only an increase in the physiolo- gical urine sugar is present the phenylhydrazin reaction may be employed which deserves wider application clinically than it receives a t present.

H.C.Jacobaeus. Cerebral Puncture andventriculography.

The lecturer reported his further experiences of cerebral puncture and ventriculography.

In case 1 an abscess in the frontal lobe of the left side had been diagnosed by means of cerebral puncture. The patient was operated upon and an abscess the size of a hen’s egg evacuated. The result was favourable a t first. Afterwards progressive encephalitis super- vened and the patient died in about 5 or 6 weeks.

Case 2 was a man of 32 who 6 months previously had had a blow across the top of his head. Subsequently symptoms of increased cerebral pressure developed without definite localisation. Cerebral puncture along the scar gave a negative result. Ventri- culography disclosed the distension of only one ventricle. The tumour was localised to a placewhere it shut off the communication between the ventricles. An operation was performed but the tumour could not be found. A t the post mortem examination