investigations on glycogen

18 Pages·2007·2.06 MB·English

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INVESTIGATIONS ON GLYCOGEN u
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BY 1
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S. VAN CREVELD, M.D. 1
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(Fronm the Propaedeutic Clinic and the Laboratory for General Pathology, /a
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University of Amsterdam.) c
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Under the title ' chronic hepatogenic hypoglyeaemia in childhood ' we 9.9
described1', some time ago a number of investigations in a boy who had o
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had a very large liver since birth. Clinically he gave the impression of 1
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adiposogenital dystrophy, and, in addition, he showed a very marked e
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disturbance of carbohydrate metabolism. The predominant features of this ru
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disturbance were chronic hypoglyeaemia in the fasting state, without the ry
usual symptoms, and accompanied by ketosis; little or no change in the 19
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blood-sugar value after subcutaneous injection of adrenalin, and hyper- 4
sensitiveness to small quantities of insulin. As a cause of this anomalous . D
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disturbance we conceived a continuation of the foetal condition, and we w
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sought in faulty glycogenolysis an explanation of the condition. Thus in lo
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our boy the ketosis and the absence of hyperglycaemic response to adrenalin de
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might not depend upon a poor glycogen content of the liver. fro
We found support for our ideas especially in the publications of m
von Gierke3'4 and Sch6nheimer5. We thought we had to deal in our boy h
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form of liver hypertrophy. The features of this hypertrophy were the .b
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accumulation of glycogen, which during life and after death could be j.c
mobilized only with difficulty. Since then the interest in ' glycogen disease o
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has-greatly increased and different authors6-12a have published definite cases o/
of ' hepatomegalia glycogenica,' which have been studied clinically. The n J
deviations in metabolism found by these authors as a whole agree with an
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those found in our case. In our opinion our case is therefore one of a
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hepatomegalia glycogenica and in thiswe are supported by the recent findings 3
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of other investigators. It is important to note that this interesting glycogen , 2
disease must be regarded as a general disease of metabolism, in which the 0
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glycogen can only be mobilized with difficulty, and may accumulate in 3 b
various organs, not only in the liver. In this way it may give rise to y g
hypertrophy of different organs. This accumulation of glycogen plays a big ue
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role in the occurrence of a number of congenital deviations and in those t. P
arising shortly after birth. Thus, it is a disturbance which merits the ro
consideration ofpaediatricians, and the study of this disturbance will increase te
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our insight into several diseases of childhood. Further, glycogen disease and te
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10 ARCHIVES OF DISEASE IN CHILDHOOD C
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Elsewhere", "' we have written more extensively upon the significance of t pu
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glycogen in the occurrence of hypertrophy of other organs than the liver lis
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(heart, kidneys, pylorus). e
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We have been able to continue our observations in this patient with the a
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large liver and to extend our researches during last year. Further, a second 1
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child, which presented almost the same morbid picture with analogous .1
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deviations in metabolism, has come under our care. We have attempted, 3
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as before, to investigate the disturbance of metabolism in this disease, and /a
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to make more exact its differential diagnosis from other chronic liver diseases, c.9
especially from the cirrhoses. .4
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B., a girl, the second case, now six years old, was a full-term child, delivered .9
spontaneously. Throughout her pregnancy the mother remained well. The child's o
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weight at birth was just over 7 lb. She was breast-fed until the age of 10 months. 1
Her weight when one year old was about 21 lb. Throughout this time the physical F
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condition remained good and there was no evidence of rickets. The mental b
development of the child was normal. Though not clinically established there is rua
much evidence to suggest that the child at birth had already a large liver. In a ry
photograph, taken at the age of 6 months, the abnormally large circumference of the 19
abdomen can be distinctly seen, and before the end of the first year the presence of 34
an abnormally large liver had been established with certainty. We know that during . D
the first year of life no peculiarities occurred. o
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After the first year of life this child, just as in the case of our first patient, n
had periodic attacks of persistent vomiting in the morning and showed also a special lo
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preference for bread. When the mother came to us with the child in January, 1932, d
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there were no other complaints aDart from this nausea and vomiting. The child was d
hindered in her movements by the enormous abdomen. The child was alert. The fro
mental development was normal and she went to a preparatory school. She had a m
good appetite, preferred bread, had no complaints of the abdomen, and no attacks h
of fever. ttp
Father normal. A1other was 37 years when the child was born, this being ://a
her 7th pregnancy and the first child of her second marriage. She had had one dc
abortion, once a still-born twin; one child died a-t the age of one year from broncho- .b
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pneumonia following measles. The other children are normal; no known enlargement
of the liver in the familv. Of the medical condition of the first husband little is j.co
known, except that he was a drunkar(l. The Wassermann reaction (Jan., 1932) m
in the mother was negative. Since the birth of the girl the mother has had no o/
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further pregnancies. No family history of tuberculosis. J
On examination (Jan., 1932) the girl, nearly 5 years old, weighed 35' lb., and was a
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only 38 in. in height. She was well nourished with normal subcutaneous fat, and ua
no suggestion of adiposity. No icterus. Colour of the skin was somewhat dark but ry
showed no pigmentation of skin or mucous membranes. No abnormal growth of hair. 3
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Rather marked dental caries. The neck was short, and on both sides were numerous , 2
small glands. The abdomen was protuberant. Heart, blood-pressure and lungs were 0
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normal. 3
The abdomen was greatly distended as a whole, and on the upper part of the by
wall of the abdomnen a fine net of veins was seen; no caput medusae. The distension of g
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the abdomen was caused by a very large liver, which occupied nearly the whole right e
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lobe of the liver could be felt from the level of the umbilicus, slanting upwards and rote
disappearing under the costal arch at about the axillary line. Just at the umbilicus c
an incisura could be felt. The liver was of firm consistence and felt smooth; its ted
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INVESTIGATIONS ON GLYCOGEN DISEASE ii C
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Tedhgeegrweaastessthacrpi.rcumNfoerepnacien oofnthpealcphaetsitonwaosf 2t1heina.badnodmenof.theNoabsdiognmsenof25friene. flTuihde. : firs
spleen could with difficulty be felt; kidneys not palpable. External genitals normal. t p
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Reflexes normal, muscular system normal; the legs slim. The child was not easily b
exhausted by exercise. lis
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The child was intellectually normal. She complained of no abdominal symptoms, e
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and showed no clubbing of the fingers. a
The urine in fasting condition contained no albumen or sugar, and showed a s 1
weakly positive reaction for urobilin, and strongly positive tests for acetone and 0
diacetic acid. Bile absent. Specific gravity normal. Nothing abnormal in the .1
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sediment. Stool: normal colour and consistency; no worms or ova; on a mixed diet 3
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the fat-content was not increased. The Pirouet, Wassermann and Weinberg reactions /a
were all negative. Temperature normal. dc
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Examinationi of the blood showed a leucocyte count of 12,700 with 5 per cent. m
eosinophils and a moderate relative lymphocytosis; no anaemia; platelets normal. j.c
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Throughout the last year the blood was investigated repeatedly with similar results; m
except that the leucocyte count was normal and the eosinophilia less. A distinct o/
leucopenia, as found in the boy, was not found. n J
X-ray investigation: no enlargement of the heart; no signs of active rickets; no a
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apparent abnormalities of the extremities with the exception of several small u
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transverse lines in the bones of the lower extremities as a sign of irregular growth; ry
some delayed ossification, in both wrists only three of the small bones were ossified. 3
gSleallnads.turcBiocnaensoromfatlh.e sKkiudlnlewyesrenornomramla;l.no abnormalities in the region of the adrenal 0, 20
Electrocardiogram normal. Basal metabolism slightly increased (two 23
determinations, +19 and -+27 per cent. At the second determination the child was b
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not quiet). g
The girl therefore showed a greatly enlarged liver without demonstrable ue
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hypertrophy of other organs, but with definitely delayed growth. Marked t. P
ketosis and slight urobilinuria were present. No signs of an endocrine ro
disturbance were found and especially no marked adiposity as was found in te
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our boy. te
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ARtcHivES OF DISEASE IN C(HILDHOOD C
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determinations ranged between 0-046 and 0059 per cent.; in the venous blood t p
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between 0-05 and 0-06 per cent. (Hagedorn and Jensen). blis
In our boy the fasting blood-sugar values now show a tendency to rise h
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(in the capillary blood 0057-0(073 per cent.). In the girl all clinical d a
symptoms of the so-called hypoglyeaemic complex as occurs in hyper- s 1
insulinism were absent. 0.1
In addition, after 25gm. of glucose the girl showed a biphasic blood-sugar 13
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curve. The blood sugar remained increased for a long time and had not /a
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returned to the fasting level after 41 hours, which in itself is strongly against c
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hyper-insulinism. The maximal elevation was only from 0058 to 0112 per .4
cen)t.; no glucosuria occurred. 9.9
After 20 gm. of fructose the fasting blood sugar rose from 0056 to a o
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maximum of 0088 per cent., i.e., a little higher than may occur normally 1
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i30 mgm. per cent.), but the increase lasted for more than two hours. The e
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urine contained no reducing substances, and the ketosis existing in the fasting ru
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condition decreased very much after giving fructose. ry
After 25 gm. of galactose no sugar was excreted in the urine. 19
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The elevation of the respiratory quotient after giving 20 gm. of glucose 4
was investigated; in one hour the quotient rose above 1, but the girl had . D
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not remained quiet. w
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ADRENALIN TEST.-After subcutaneous injection of 0-5 mgm. of adrenalin lo
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the girl showed only a very slight elevation of the blood sugar: in the first e
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test from 0054 to 007 per cent., in the second test from 0051 to 0-066 per fro
cent. But a markedly increased excretion of ketones after the adrenalin m
injection was noticed. In our boy. although his fasting blood sugar is h
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0-069 to 0072 per cent. occurred within two hours after the injection. .b
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In view of the adrenalin effect our idea of the cause of the blood-sugar j.c
elevation after adrenalin injection must be reconsidered. The Coris'" have om
demonstrated in different ways that the blood-sugar elevation which normally, o/
occurs after adrenalin injection, is only partly caused by mobilization of n J
liver glycogen and this only in so far as the primary elevation is concerned. an
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In speculating as to the existence of a glycogen depot in the liver which can a
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be mobilized, stress must therefore, a priori, be laid upon the non-appearance 3
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of this initial elevation. , 2
In both our patients, however, it appeared that the adrenalin effect was 0
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also abnormal in so far as the rise of the lactic acid content of the blood, 3 b
which normally accompanies adrenalin hyperglyeaemia and which is related y g
to an increased splitting of muscle glycogen, was only very small. ue
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In this connection we wish to point out the disturbance of glycogen t. P
splitting and of lactic acid formation in muscle, which occurs after extirpation ro
of the adrenals and is accompanied by an increased consumption of creatine te
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phosphoric acid. It appeared that creatine was present in the urine of both te
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our children, but in an amount normal for their age. b
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INVESTIGATIONS ON GLYCOGEN DISEASE 13 C
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be deIvniasttiilnlganfortohmernowramyalt.he aWdhreennaliinn nefofremctalinmbeonthsouubrcucthainledoruens aipnjpeecatrieodn toof : first p
adrenalin is combined with oral administration of glucose in an amount u
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normally used for tolerance tests, then the elevation of the blood sugar is lis
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for the most part much more marked than after adrenalin injection or glucose e
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ingestion alone (Burkens). This is apparently a consequence of the second a
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adrenalin effect, that is, a decrease of sugar consumption in the muscles by 1
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which the extra glucose given orally causes a higher elevation of the blood .1
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sugar. In both our patients such a test has been done once. In both cases 36
the elevation of the blood sugar after adrenalin injection together with /a
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glucose ingestion, was only slightly greater than after glucose ingestion alone. c.9
From investigation of the protein spectrum of the blood serum it .4
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appeared that the very important increase of the globulin content of the .9
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serum which is present in the majority of chronic parenchymatous liver n
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affections1" was absent in both our patients (compare the two control cases F
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in Table 1). b
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TABLE 1. a
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PR.OTEIN SPECTRUM OF BJLOOD PLASMA. 1
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(Percentage figures) 3
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Glycogen liver . D
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Normal w
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Pat. B. Pat. lo
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Total protein..1 6.5 - 8 I83-t 7.63 .. 902 914 d fro
Albuimen . 45 - 5.5 526 4.66 502 4.2 4.11 m
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Globulin .. 18 - 2 4 269 252 2-09 428 4S ttp
Fibrinogen -. 0.25 - 0.3S 0.39 0*!5 . 0.54 024 ://adc
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'AkText.L w--i.tLIh tLIhe serum ofLI b1-o-jtL'hL pa-tjLi-e'-n-.tjsL- we performed-3 t-iLhILe n13loccu-lIa--tiLiIon t.est. j.c
which according to modern investigations is always positive in chronic om
parenchymatous liver affections (the so-called Takata-Ara reaction)1 7. In o/
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our boy E. the test was negative, in the girl B. it was only weakly positive. J
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Corresponding to the protein spectrum of the serum the sedimentation- n
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rate of the erythrocytes of both our patients in the defibrinated blood as well a
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as in the non-defibrinated blood was normal. 3
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Certain determinations of different constituents of blood and blood , 2
serum have also been made in both our patients. Table 2 gives a survey 02
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of the results. From this it appears that in the girl as well as in the boy b
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there was a marked elevation of the cholesterol content. In both our g
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patients the relation between free cholesterol and cholesterol esters, a relation e
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which in liver diseases is often changed, was normal. There was no decrease t. P
of cholesterol esters. In both our patients with hypoglycaemia the non-sugar ro
reducing fraction and glutathion content (Groen) were normal. It further tec
appeared that the lipolytic activity of the serunm Qf both our patients wtas ted
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14 ARCHIVES OF DISEASE IN CHILDHOOD C
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balesoprneosremnatl.in Itnheadsdeitriuomn,ina pchairneinnec-h,ymaantdouasn altiovxeyrl-arnedsisptaannctreliapsaseaff(eacstimoansy) : first p
were absent from the serum. u
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TABLE 2. he
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SONME CONSTITUENTS OF Bl<.OOI) SERUM. a
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.I- 1
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Pat. E. Pat. B. Normal .1
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Per cent. Per cent. Per cent. 3
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/a
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Cl in total blood 0.29 0294 0-27- 0.30 .9.4
Cl in serum 0.38 0-37 035- 040 9
Ca in serum 12.56 mgm. 10-70 mgm. 7-8 -11-9 mgrn. .9 o
Ca in serum ultrafiltrates 8-376 nigm. 4.86- 6.41 mgm. n
Mg in serum... 2503 mgm. 135 - 3 rngm. 1 F
Mg in serum ultra filtrates 1-695 mgmn. 2 mrg.r e
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Inorganic P in blood 4-5 mgnm. 3 8 mgin. 25 - 4 mgm. ru
Clholesterol in blood 200-263 mgi. 210-221 man. 160 -180 mgm. a
ry
Cholesterol in serum 286-333 mgm. 206-294 mgm 180 -200 ngm. 1
Free cholesterol 35-5 41 30 -40 9
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Cholesterol esters 64'5 59 60 -70 4
Non-sugar reducing fract.i(,n 273 nmi,m 28 mgm. 22-28 mum. . D
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Giutathlon 34 mgm. 31 mgm. 25 -10 mgm. w
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Bilirubin 1-08 urits lo
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GLYCOGEN METABOLISM.-Duriiig the last year we studied in different fro
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ways the glycogen metabolism of both our patients; firstly, the so-called h
initial insulin hyperglyeaemia which when present would prove the existence ttp
of a glycogen depot. The effect is not given by pure insulin prepara- ://a
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tions18. Using an insulin preparation of Burroughs Wellcome -& Co.. which c
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in animal experiments was proved to produce an initial rise in blood sugar, m
we found no such effect in our girl (Table 3). The absence of this effect in j.c
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TABLE 3. o/
INVEiTI(GATION AFTEIS THlE SO-CALLED INSINIAI JIYPEfl.(I.Y(,CAI 1IA. n J
- - Blood sugar in mgm. per cent. I~~M~~~aximal anu
Before After3) 10 15 20 23 30 elevation ary
Minutes percent. 3
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219 , 2
Normal ... ... ... 91 99) 111 101 79 4,) ... 21-9 02
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Patien1tB.... 38 )1 48 37 42 ... b
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Liver cirrhosis ... 93 9,3 86 74 54 34 43 0 e
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Scvere iaundice 92 92 88 81 72 63 530 0 t. P
ro
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Rccovered jaundice *.. 79 97 88 68 47 41 47 227 c
... te
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INVESTIGATIONS ON GLYCOGEN DISEASE 15 C
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the boy E. The same holds true for the influence exerted by insulin in lis
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vitro on the oxidative glucose fermentation by erythrocytes"' of our patients. e
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For this investigation we made use of a pure insulin preparation kindly a
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provided by Prof. Laqueur. 1
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The quantity of diastase in blood and urine of both patients proved to .1
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be normal. An increased diastase excretion in the urine, as found by some 3
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investigators, was not found by us. Again, the so-called diastase-fortifying /a
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action of the blood serum2, by which is meant the smallest quantity of c.9
serum which in vitro exercises a fortifying action on a pancreatic amylase, .4
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was normal in both our patients. .9
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Special attention was paid to the glycogen in the blood of our patients. n
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Could this glycogen be split? Little is known up to the present regarding F
the glycogen of the blood. According to Gabbe l, in the normal blood the eb
glycogen should, even on keeping for several hours at 370 C., decrease only rua
very slightly, notwithstanding the presence of a glycogenolytic ferment. ry 1
Thus the blood glycogen should in this stability resemble the glycogen 9
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present during foetal life, and differ in this respect from that present in liver 4. D
and muscle, corresponding to that existing in liver and different organs in o
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glycogen disease. n
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With our method, which could be regarded as a micro-modification of a
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Pfluiger's method, we had obtained for the glycogen content of the blood of ed
the boy E. some results which could be called distinctly high. Since then fro
we have paid special attention to the method of determination of blood m
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glycogen and we have elaborated a method which certainly will be of ttp
importance in the future. Our method is as follows:- ://a
DETERMINATION OF GLYCOGEN TN I C.C. OF BLOOD).-1 c.c. of blood is haemolysed by dc
adding 1 c.c. of distilled water in a wide Pyrex centrifuge tube with a ground glass .b
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hsteoaptpeedr.inTawoboicluibnigc wceantteirmebtartehs ofofr6015n-e2r0 cmeinntu.tKesOaHndarecaraedfdueldlyasnhdatkheencflroosemdttiumbeetios j.co
time. After cooling, 8 c.c. of distilled water and 16 c.c. of absolute alcohol or 96 per m
cent. alcohol are added and the contents of the tube carefully mixed. The precipitated o/
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glycogen is allowed to settle overnight. After centrifuging, the precipitate is washed J
at least twice with 66 per cent. alcohol. The glycogen is determinated as glucose by an
hydrolysing with 4 c.c. 2'2 per cent. HCI for two hours, after evaporation of the ua
remaining alcohol. The material is now neutralised with 2N. NaOH using phenol ry
red (one drop) as indicator. The glucose is determined after the method of 3
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Hagedorn and Jensen. The whole determination is thus carried out in the same tube. , 2
In our earlier investigations we did not haemolyse the blood and this is probably 0
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the reason whv our double determinations did not always correspond. The change 3
in the time of boiling with KOH from two hours to 15-20 minutes we obtained from by
the recent publication of Good, Kramer and Somogyi22. For the rest we still follow g
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the method described above with excellent results; the method was tested using e
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we have constantly found in the fasting blocd of both our patients values cte
which we look urpon as high. no leucocytosis being present which could causs d b
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16 ARCHIVES OF DISEASE IN CHILDHOOD C
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t1h4ismoenltevhastiwoenr.e aTshfeolrlewssu:l-tsGloyfcoagesenricesontoefntdeotferbmlionoadti(oanssmgdumr.ingglutchoesepapsetr : firs
100 c.c. of blood): Patient B. 23-75, 23, 20, 19-25, 21-25, 18-75, 21-35, 21, t pu
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mean value, 21 04; Patient E. 26, 25, 23-05, 27-5, 22-9, 26-62, 26-25, 24, 28, lis
25, mean value, 25-43. Next (Table 4) we give the results obtained in a he
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TABLE 4. .1
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(4ILYCOGENT CONTENT OF THE BLOOD. 6
/a
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(expressed asglucose in mgm. percent.) c
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35 determinations in children: Examples 9
8 showed, 5-10 Cong. pyloric stenosis ... 102 .9 o
14 ,, 10-15 13 n
10 ,, 15-17 Premature inifants ... ... 13-17 1 F
2 ,, 17-2(0 166 e
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1 ,, 20-22 2125 ru
Hypertrophy of the heart in a
Blood from umbilical cord: patent interventricular ry 1
13 determinations: septum ... ... 15-75 9
3
4 showe(d 5-10 10 4
v 7 ,, 10-15 Cyclic vomiting ... ... 16 . D
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2 ,, 15-17 13-33 w
Microcephaly ... ... 18-75 nlo
Coeliac disease ... ... 12 a
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Determinations in adults: fro
Addison'sdisease ... 7.06 Myelogenous leukaemia 71 m
CLiurershohseipsathiespatis ...... 11227--361282 RIre.ns(au1ll5i0nr,-i0rc0eks0eitswsthainttecell.s.). 486--5)35 http://a
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17-4 diabetes 13*3 c
ConcesteA liver ... 16-75 .bm
26/1 j.c
Pregnancy ... ... 18 om
(holelithiasiis ... 12-45 o/
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number of children some of whom were healthy, the others suffering from ua
varying diseases; a number of determinations also were made in blood from ry 3
the umbilical cord and are noted in this table. In children under 12 years 0, 2
of age, as is reported in the table, with the exception of our patients, we 0
2
found by our method only one glycogen value above 20 mgm. per cent., and 3
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that in a premature child; as a rule the value was much lower. We also y
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once found a value above 20 mgm. per cent. in a child with miliary u
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tsuabyeirncgultohsaist.theOneletvhaetsieongroofuntdhse gwleyctohgiennk cwoenteanret joufsttihfieedblporoodvisisionofallsyomien st. Pro
diagnostic significance in the diagnosis of hepatomegalia glycogenica. We te
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say ' provisionally ' because blood ^n with othes forr livir te
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INVESTIGATIONS ON-GLYCOGEN DISEASE 17 C
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hypertrophy was not available. We were able to examine the blood of : firs
adults with marked liver hypertrophy. A priori we are not justified t p
in comparing these values with those obtained -in children with liver u
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hypertrophy and especially with those obtained in our patients, because lis
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the glycogen metabolism in childhood occupies a separate place, as has been ed
shown clinically and experimentally. In adults with liver hypertrophy a
s
values as found in our children also occur. When the number of leucocytes 1
0
is greatly increased, this in itself may be the explanation of a marked .1
1
elevation of the glycogen content. In an adult female patient with myeloid 36
leukaemia and a large liver (150,000 leucocytes) we found a very high /ad
c
glycogen content of the blood in two determinations, 485 and 71 mgm. per .9
cent., expressed as glucose. .49
Incidentally it may be noticed that according to the table the glycogen .9 o
increase did not occur in two cases of pyloric spasm, an affection in which n
1
an accumulation of glycogen must be considered as a possible cause of the F
e
hypertrophy. Further, we recently found in the case of a baby where at b
ru
the autopsy histological and histo-chemical, and later on chemical a
investigation revealed an accumulationi of glycogen in the heart muscle ry 1
(idiopathic hypertrophy of the heart, vide infra), that the blood obtained 93
4
after death contained 18 mgm. per cent. of glycogen, a value which in our . D
experience is at the highest limit of the normal values. The fluid with o
w
which the organs were bathed at autopsy contained however already n
lo
87 mgm. per cent. of glycogen. It is improbable that cases of glycogen ad
e
disease, where hypertrophy does not primarily concern the liver, should d
show analogous deviations in metabolism to our patients. Little can at fro
m
present time be said about the glycogen of the blood in such cases. h
In Table 4 we give some results obtained in adults suffering from diseases ttp
in which the carbohydrate metabolism was specially concerned. ://a
d
As to the splitting of the glycogen of the blood we agree with Gabbe in c
.b
judging that this glycogen can be split only with difficulty. Blood was m
collected with aseptic precaution and received in sterile tubes. After j.c
o
incubation for 1- hours at 370 C. the blood of our patients showed no m
splitting of its glycogen. In normal children the blood glycogen not o/
n
uncommonly shows marked splitting in the same time. In keeping this J
a
normal blood for 48 hours at 370 C. we constantly found that a definite nu
a
but varying decrease of the glycogen content could be demonstrated ry
and in this we differ from Gabbe. In our patients the decrease of 30
the glycogen content of the blood under the same conditions which are so , 2
0
favourable for splitting, proved to be smaller than the mean decrease in the 23
control patients and it scarcely agreed with the lowest values found in control b
y
children (Table 5). g
u
Further, we found that glycogen added to serum of our patients and to es
serum of control patients was split by both in the same degree and in the t. P
same time. ro
te
Ot- ,Nt -step w-s to -RI¶ f .hether by mixing the blood of our cte
patients Ii .'at of co' id keeping it for 48 hours at 370 C. d b
y
B c
o
p
y
rig
h
t.
A
rc
h
D
is
18 ARCHIVES OF DISEASE IN CHILDHOOD C
h
ild
the splitting of the blood glycogen of our patients could be accelerated. : firs
Increased glycogenolysis was not constantly found, however, so that t p
provisionally we are not justified in concluding, as we thought at first, that ub
lis
h
TABLE 5. ed
GLYCOGEN VALUES OF BLOOD DETERMINED DIRECTLY AND AFTER INCUBATION FOR 48 HOUJRS a
s
AT 370 C. EXPRESSED IN MOM. GLUCOSE PER 100 C.C. OF BLOOD. 1
0
.1
Controlpatients Immediate After 48 hours at 370 C. Decrease in per cent. 13
6
/a
d
c
21 ...... ...... 1135--7755 1100--525 23534363 .9.49
43 ... ...... 1176*-475 129-.681 2462--4638 .9 on
56 ...... ...... 1115--7755 56.-55'' 5538--273 1 Fe
7 10 5-5J 45 b
8 15-62 7-375 52-79 rua
190 ...... ... 1128-12 138-75 2334-6 ry 19
11 ... ... 12.62 8 36-6 34
. D
mean doer. 39-26 o
w
n
Patient E lo
a
1 24 19-25 20 d
... e
2 28 24*25 134 d
3 o.f... 25 19 24 fro
m
mean deCr. 19-1 h
ttp
Pati1ent B 21-25 16-5 22.25 ://a
... d
2 ... 23-1 18*75 19 c.b
m
maen deCr. 20-62 j.c
o
m
there exists in normal blood a substance which favours the splitting of the o/
n
blood glycogen of our patients. J
a
In summarizing (Table 6) the above results of the clinico-chemical n
u
investigation, we found in both cases, in addition to our former findings in ary
our boy:- 3
0
1. A combination ofhypoglycaemia and ketosis in the fasting condition. , 2
0
2. An abnormal adrenalin effect, expressing itself by:- 2
3
a. Absence of a distinct elevation of the blood sugar. b
y
b. A marked increase of the ketosis. g
u
c. Only a small elevation of the lactic acid content of the blood. es
3. An abnormal blood sugar curve after ingestion of glucose, t. P
unaccompanied by glycosuria. ro
te
4. No diminution in tolerance to galactose and fructose. c
te
5. Absence of the so-called initial insulin hyperglyeaemia. d
6.. a. Normal values for the diastase activity of blood and urine, by
c
b. Normal diastase activating effect of the serum. o
p
y
rig
h
t.