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OBSERVATIONS UPON BILIARY DRAINAGE
608
DR. T. HUNT : BILIARY DRAINAGE
(Table II.). A gall-bladder containing stones may empty its contents normally with no symptoms or discomfort, and this is of interest in relation to the causation of symptoms in cholelithiasis. As a rule, however, there is considerable discomfort, and sometimes severe pain over the gall-bladder and in the right hypochondrium and epigastrium, during the
OBSERVATIONS UPON BILIARY DRAINAGE BY THOMAS HUNT, D.M. Oxon., F.R.C.P. Lond. PHYSICIAN TO OUT-PATIENTS, ST. MARY’S HOSPITAL, LONDON ; LATE MACKENZIE-MACKINNON RESEARCH FELLOW
MUCH has been written on the technique and also the diagnostic and therapeutic uses of biliary drainage. The present paper, based on over 100 cases in which it was used, makes no claim to review all these aspects of the subject. The group of cases analysed are selected from a much larger number, and form a series in which the diagnosis was definite and the biliary stimulus always the same-namely, 50 c.cm. of 33 per cent. warm magnesium sulphate solution. Any cases in which the position of the tube in the duodenum has been uncertain have been excluded, and in some the drainage has been performed twice or even three times if the result has been doubtful. Biliary drainage has been carried out, first, on a number of persons whose biliary and hepatic systems was presumably healthy. A few of these have had no illness ; the others have been sufferers from arthritis (12), hyperthyroidism (5), iridocyclitis (5), Meniere’s disease (2), and neurosis (5). For purposes of comparison I have regarded these as normals. It might be supposed that the rate and volume of biliary flow would enable us to draw conclusions about biliary disease, comparable to those we draw from the flow of urine. That hope, however, has not been fulfilled. The onset and the amount of flow after the introduction of the stimulus give little indication whether disease is present or not (Table 1.). on
TABLE
I.-Average Onset, Bate, and Bile-flow (74 Cases)
Even with
a
cirrhosis)
bile
Volume
of
seriously damaged liver (e.g., in advanced is secreted after the injection of magnesium sulphate in about normal quantity after the normal latent period and at about the normal rate. On the other hand, the flow is certainly much faster after removal of the gall-bladder, and this suggests that the quantity and rate of flow, after the dose of magnesium sulphate, is governed less by the organic condition of the liver than by some controlling influence of the gall-bladder ;the normal response to the introduction of magnesium sulphate the gall-bladder and seems to be an emptying of and is not liver, wholly dependant upon liver secretion. Similarly it might be hoped that the symptoms produced by reflex stimulation of the biliary flow would give some indication of disease in the gallbladder when this contracts and empties its contents. The symptoms, however, prove no certain guide
flow. Patients who have had their gall-bladders removed are particularly apt to have severe nausea, ,
TABLE II.-Reaction to Introduction J.l1agne8ium Sulphate into Duodenum
(50 c.cm.
*
of 33 per cent.
of Warm (133 Cases)
solution)
Nausea, pain, discomfort, vomiting.
discomfort, or vomiting while the flow is in progress. Also symptoms are about twice as common in chronic cholecystitis, and about four times as common in the presence of stones, as they are in the normal subject. Hence the course of the drainage should be carefully watched and noted. In severe cirrhosis of the liver there is rarely pain or discomfort, and in only 4 patients out of 21 suffering from hepatic disease was there vomiting during or immediately after the flow of bile. Undue stress should not, however, be laid on these findings, owing to the unavoidable psychological effect of carrying out the test. (Special care was taken in these cases not to let the patient think that anything other than water was being injected down the tube.) It is known also that symptoms may vary with the type of stimulus employed so that from the diagnostic point of view results in different hands may be difficult to compare. Another fact that is remarkable is that such a relatively large dose of magnesium sulphate introduced direct into the duodenum-about 4 drachms of the salt-causes nausea or discomfort in less than 1 in 5 normal subjects ; and if the bile is removed by the tube it seldom produces much diarrhoea. The same dose introduced into the stomach usually causes profuse diarrhoea and, as would be expected, more nausea and vomiting. This observation suggests that part at least of the purgative effect of magnesium sulphate is dependant either upon the increased flow of bile into the intestine or upon the effect of the salt in the stomach where it may set up gastrocolic stimulation either chemically or reflexly. Complete failure to obtain any bile after introduction of the magnesium sulphate is very rare, provided care is taken to ensure the correct position of the tube. In five patients only have I noted complete absence of any reflex biliary flow to this stimulus, though in no case was the test abandoned under 35 minutes, and in most cases not till a longer time had elapsed. (In 3 of these cases 1 c.cm. of pituitrin given subcutaneously also failed to bring about withdrawal of bile from the tube.) In all these there
609
DR. T. HUNT : BILIARY DRAINAGE
doubt about the position of the tube, but the only response to the introduction of the usual stimulus was a slow secretion of 15-20 c.cm. of thick mucoid white fluid, strongly alkaline, which I regard as pancreatic in origin. Four of these five patients showed a curiously similar clinical picture. Three were female and one male. All were very neurotic and all complained of long-standing upper abdominal discomfort, with attacks of severe pain amounting to true colic, coming on two or three hours after food. Three of them were woken about 2 A.M. with severe pain, and all stated that they could not eat eggs or fat without discomfort or pain. In two cases the symptoms had followed a severe mental shock. Only three of these patients were radiographed after administration of tetraiodophenolphthalein by mouth and of these two showed no shadow of the dye ; the third gave a normal concentration. One of the patients showing no dye shadow was operated upon later and the report was " enlarged gall-bladder ; no stones; no inflammatory changes. Cystic duct constricted. Cholecystectomy performed." In this patient an eight-hour residue in the stomach was also shown by barium meal, without any evidence of any organic was no
lesion. I think that these five patients almost certainly belong to the group of functional spastic dyskinesias of the
due to in and the absence of obstructive causes, jaundice complete failure to obtain any bile is suggestive of such functional disorder of the biliary
gall-bladder (Westphal, Newman),
nervous
passages. TABLE III.-Concentrated " B " Bile
"
"
B normal concentrated bile. This is a highly characteristic finding in liver disease, and I have noted it in 7 cases of cirrhosis of the liver (4 of which were proved by operation). Such a combination is likely when the liver is so diseased that it fails to pick out a
TABLE IV.-Oral
Cholecystography
and
Biliary
Drainage
* 8 cases : 1 cholecystitis (oper.), 3 cholecystitis (7), 3 migraine, 1 normal. t 8 cases : 7 cirrhosis of liver, 1 migraine.
the opaque
dye from the portal circulation in sufficient concentration, whereas biliary concentration in the gall-bladder (being healthy) is unimpaired so that dark " B bile is obtained by drainage. The use of "
the two methods in combination may therefore be worth while where cirrhosis of the liver is suspected.
A further characteristic feature of severe cirrhosis of the liver is the striking appearance of the bile which has a bright red colour, unlike the normal yellow, brown, or dark mahogany tinge. As regards the chemical, microscopic, and bacteriological findings in bile, I only propose to mention two points. The first refers to the significance of crystals on microscopic examination, since some writers have regarded the findings of both cholesterol and pigment deposits together as pathognomonic of gall-stones (Bochus). Thus Piersol records that all his cases in which both crystals were found proved to have calculi ; of 40 patients investigated by R4sky, in whom both types of crystals were found in the bile, only 1 showed no calculi or cholecystitis at operation. The observation is one of considerable diagnostic importance, but there are a few records of the incidence of these crystals in the bile of normal
people.
Table V. shows the microscopic findings in my patients, in all of whom the bile was examined soon after withdrawal-just as urine must be examined if TABLE
"
V.-Crystalline Deposits
in Bile
(91 Oases)
"
Failure to withdraw any concentrated B bile, which comes at least in part from the gall-bladder itself, has very much less significance however (again in the absence of obstructive jaundice). From Table III. it will be seen that in over 10 per cent. of normal subjects no gall-bladder (or " B " bile) was found. In none of 10 patients subjected to biliary drainage at periods from 3 months to 14 years after cholecystectomy was any true concentrated " B" bile obtained, though certain workers state that it may be recovered in a proportion of such
patients (Martin). In only about a quarter disease have I obtained " B " bile.
of the a
cases of gall-bladder normally concentrated
when " B " bile is not obtained, the cholecystographic shadow is below normal; but there is a divergence of some 30-40 per cent. in my cases both in patients showing a normal shadow and those giving no shadow or an abnormally faint one. (Table IV.). The second group shows the diagnostic significance of a positive cholecystogram (absent or very faint shadow) combined with the withdrawal of As
a
rule,
is to be attached to crystalline deposits. In 9 out of 43 (21 per cent.) of my presumed normal subjects both types of crystals were present ; they were also found in 10 out of 13 cases of proved gallstones. (I have not attempted any quantitative comparison of the numbers of crystals.) From this it seems that the coexistence of cholesterol and
significance
610
DR. B. J. BOULTON : AGRANULOCYTIC ANGINA
calcium bilirubinate crystals cannot be regarded as pathognomonic of gall-stones, though strongly suggestive of that condition. It is significant that the proportion of cases showing both types of crystals was about the same after cholecystectomy (almost always for gall-stones) as in subjects of cholelithiasis which implies that there is some underlying abnormality of the bile in gall-stone subjects, apart from inflammatory changes in the gall-bladder itself. The last point concerns the significance of protein in the bile, as tested by the very rough Esbach’s estimation. I have found 0’5 part per 1000 represents an empirical normal level, and that the level is increased in more than half the cases of cirrhosis and other diseases of the liver, and also in about the same proportion of cases of gall-bladder disease. It appears that a marked increase of albumin in the bile may be due either to alteration in the secretion of bile by the liver, or to its concentration by the gallbladder. In a number of migraine patients showing a dense shadow by cholecystography-which means that the concentration of gall-bladder bile is increased -the protein content of the bile was particularly
high. I do not think the protein content of the bile is of practical value in the diagnosis of gall-stones or cholelithiasis. In all cases the figures refer to the protein estimated in the most concentrated specimens of bile obtained in each case, though there is usually little difference in this respect between the various fractions of bile removed. SUMMARY
(1) Observations upon biliary drainage in over 100 cases, using magnesium sulphate as a stimulus, are recorded. (2) The rate and volume of biliary flow gave no indication as to the condition of the liver, gall-bladder, or biliary passages. (3) Pain, nausea, and other symptoms were observed during the flow of bile in 16 per cent. of normal subjects, but more frequently in the presence of gall-bladder disease. (4) Failure to obtain any bile by drainage, in the absence of jaundice, was rare (5 cases only) ; dyskinesia of the gall-bladder is suggested as a cause in some of these patients. (5) In 10 per cent. of normal subjects and 75 per cent. of cases of gallbladder disease (6) Results are
no
" B " bile could be withdrawn.
compared between oral cholecystography and biliary drainage in 45 cases ; failure to visualise the gall-bladder by oral cholecystography, in association with the finding of " B " bile by drainage, was found to be characteristic of liver disease. (7) Calcium bilirubinate (pigment) and cholesterol crystals were found together in the bile in 21 of normal subjects and 77 per cent. of gall-stone subjects. My thanks are due to the trustees of the MackenzieMackinnon Research fellowship ; also to Dr. H. Orton and Dr. Courtenay Gage for very kindly carrying out the
radiographic examinations, and to St. Mary’s Hospital for allowing patients under their care.
my me
colleagues at investigate
to
REFERENCES
Bockus, H. L., Shay, H., Willard, J., and Pessel, J. F. : Jour. Amer. Med. Assoc., 1931, xcvi., 312. Chiray, M., and Lebon, J.: Le Tubage Duodenal, Paris, 1924.
Einhorn, M. : The Duodenal Tube, Philadelphia, 1926. Martin, L. : Arch. Internal Med., 1927, xxxix., 356. Newman, C. : THE LANCET, 1933, i., 785. Piersol, G. M., Bockus, H. L., and Shay, H. : Amer. Jour. Med. Sci., 1928, clxxv., 84. Rafsky, H. A. : Amer. Jour. Med. Sci., 1933, clxxxv., 851. Schemensky, W.: Deut. med. Woch., 1926, lii., 2155. Westphal, K., Gleichmann, F., and Mann, W.: Gallenwegsfunktion und Gallensteinleiden, Berlin, 1931.
A CASE OF AGRANULOGYTIC ANGINA
BY B. J.
BOULTON, M.B. Brist.
ASSISTANT RESIDENT MEDICAL OFFICER, HAM GREEN HOSPITAL AND SANATORIUM, BRISTOL
A WOMAN aged 47, unmarried, was admitted to Ham Green Isolation Hospital (Bristol Public Health Department) on May 24th, 1935, the case being
notified
as one
of
suspected faucial diphtheria.
History of illness.-She first consulted her doctor on April 2nd, 1935, complaining of a sore-throat which developed by the 5th into a definite follicular tonsillitis. Swabs taken were returned negative. The throat condition did not clear up until April 14th. On May 21st there was a recurrence rather worse than the previous attack, which rapidly became more severe. On May 23rd an area of inflammation appeared on the dorsum of the left hand. On admission (May 24th) the general condition was poor and the patient appeared to be acutely ill. The temperature was 103° F., the pulse-rate 128, and the respirations 28. Tongue furred. The fauces showed yellow semimembranous sloughs with very little inflammatory reaction apart from narrow areas of erythema around each. Heart sounds poor, lungs normal; the spleen was not palpable and there was no jaundice. The urine contained a trace of albumin. The lower part of the nose was inflamed and swollen, and the dorsum of the left hand and lower
forearm showed a large inflamed area with a blackish superficial necrosis and no attempt at pus formation. The surrounding tissues were soft. Antistreptococcal serum (20 c.cm.) together with antidiphtheritic serum (800 units) was administered intramuscularly. Progress.-By the following day (May 25th) there was no improvement in the patient’s condition and the possibility of this being a case of agranulocytic angina was discussed. A leucocyte count gave a figure of 625 per c.mm. Examination of blood films revealed an obvious neutropenia ; some of the smears showed less than a dozen white cells in all and these were chiefly lymphocytes. A differential count, based on 50 cells only, resulted as follows :6 % Polynuclears 6 % Transitionals Small lymphocytes .. 66 % 0% Eosinophils 0% Large lymphocytes.. 22 ....
....
Arneth count
%IBasophils
....
....
Red cells appear normal.
impossible.
As supplies of pentose nucleotide were not immediately available, sodium nucleinate in doses of gr. were
intramuscularly at four-hourly intervals. (after 12 doses of sodium nucleinate) the leucocyte count gave a figure of 2813 per c.mm.
administered On May 27th
total and the differential count was as follows 51% I Eosinophils Polynuclears Small lymphocytes ..16’5% Large lymphooytes .. 23’0 % Myelocytes ....
Transitionals
....
..
....
Basophils
0%
.... 0% ....
6’0 %
3’5 % I
Class1
Arneth count
:-
1’1
2
..
Arneth index 93’5% Red cells show early ansenua.
..
7% 3
..
4..5 1% 5
Several normoblasts
seen.
These results, however, did not appear to coincide with any improvement in the general condition of the patient who rapidly became worse and died on May 28th. Pentose nucleotide injections in 10 c.cm. doses had been commenced on
the
previous day. Unfortunately,
to carry out
a
it
was
not
possible
post-mortem examination.
unable to obtain any evidence in this of amidopyrin as an exciting cause. There was, however, an obvious focal infection of dental origin. It is doubtful if an earlier administration of pentose nucleotide would have affected the ultimate issue of an acute fulminating case such as this, with a total leucocyte count below 1000.
We
case
are
of
a
previous ingestion
I am indebted to Prof. I. Walker Hall for the blood counts and examination of the films.
DR. T. HUNT : BILIARY DRAINAGE
(Table II.). A gall-bladder containing stones may empty its contents normally with no symptoms or discomfort, and this is of interest in relation to the causation of symptoms in cholelithiasis. As a rule, however, there is considerable discomfort, and sometimes severe pain over the gall-bladder and in the right hypochondrium and epigastrium, during the
OBSERVATIONS UPON BILIARY DRAINAGE BY THOMAS HUNT, D.M. Oxon., F.R.C.P. Lond. PHYSICIAN TO OUT-PATIENTS, ST. MARY’S HOSPITAL, LONDON ; LATE MACKENZIE-MACKINNON RESEARCH FELLOW
MUCH has been written on the technique and also the diagnostic and therapeutic uses of biliary drainage. The present paper, based on over 100 cases in which it was used, makes no claim to review all these aspects of the subject. The group of cases analysed are selected from a much larger number, and form a series in which the diagnosis was definite and the biliary stimulus always the same-namely, 50 c.cm. of 33 per cent. warm magnesium sulphate solution. Any cases in which the position of the tube in the duodenum has been uncertain have been excluded, and in some the drainage has been performed twice or even three times if the result has been doubtful. Biliary drainage has been carried out, first, on a number of persons whose biliary and hepatic systems was presumably healthy. A few of these have had no illness ; the others have been sufferers from arthritis (12), hyperthyroidism (5), iridocyclitis (5), Meniere’s disease (2), and neurosis (5). For purposes of comparison I have regarded these as normals. It might be supposed that the rate and volume of biliary flow would enable us to draw conclusions about biliary disease, comparable to those we draw from the flow of urine. That hope, however, has not been fulfilled. The onset and the amount of flow after the introduction of the stimulus give little indication whether disease is present or not (Table 1.). on
TABLE
I.-Average Onset, Bate, and Bile-flow (74 Cases)
Even with
a
cirrhosis)
bile
Volume
of
seriously damaged liver (e.g., in advanced is secreted after the injection of magnesium sulphate in about normal quantity after the normal latent period and at about the normal rate. On the other hand, the flow is certainly much faster after removal of the gall-bladder, and this suggests that the quantity and rate of flow, after the dose of magnesium sulphate, is governed less by the organic condition of the liver than by some controlling influence of the gall-bladder ;the normal response to the introduction of magnesium sulphate the gall-bladder and seems to be an emptying of and is not liver, wholly dependant upon liver secretion. Similarly it might be hoped that the symptoms produced by reflex stimulation of the biliary flow would give some indication of disease in the gallbladder when this contracts and empties its contents. The symptoms, however, prove no certain guide
flow. Patients who have had their gall-bladders removed are particularly apt to have severe nausea, ,
TABLE II.-Reaction to Introduction J.l1agne8ium Sulphate into Duodenum
(50 c.cm.
*
of 33 per cent.
of Warm (133 Cases)
solution)
Nausea, pain, discomfort, vomiting.
discomfort, or vomiting while the flow is in progress. Also symptoms are about twice as common in chronic cholecystitis, and about four times as common in the presence of stones, as they are in the normal subject. Hence the course of the drainage should be carefully watched and noted. In severe cirrhosis of the liver there is rarely pain or discomfort, and in only 4 patients out of 21 suffering from hepatic disease was there vomiting during or immediately after the flow of bile. Undue stress should not, however, be laid on these findings, owing to the unavoidable psychological effect of carrying out the test. (Special care was taken in these cases not to let the patient think that anything other than water was being injected down the tube.) It is known also that symptoms may vary with the type of stimulus employed so that from the diagnostic point of view results in different hands may be difficult to compare. Another fact that is remarkable is that such a relatively large dose of magnesium sulphate introduced direct into the duodenum-about 4 drachms of the salt-causes nausea or discomfort in less than 1 in 5 normal subjects ; and if the bile is removed by the tube it seldom produces much diarrhoea. The same dose introduced into the stomach usually causes profuse diarrhoea and, as would be expected, more nausea and vomiting. This observation suggests that part at least of the purgative effect of magnesium sulphate is dependant either upon the increased flow of bile into the intestine or upon the effect of the salt in the stomach where it may set up gastrocolic stimulation either chemically or reflexly. Complete failure to obtain any bile after introduction of the magnesium sulphate is very rare, provided care is taken to ensure the correct position of the tube. In five patients only have I noted complete absence of any reflex biliary flow to this stimulus, though in no case was the test abandoned under 35 minutes, and in most cases not till a longer time had elapsed. (In 3 of these cases 1 c.cm. of pituitrin given subcutaneously also failed to bring about withdrawal of bile from the tube.) In all these there
609
DR. T. HUNT : BILIARY DRAINAGE
doubt about the position of the tube, but the only response to the introduction of the usual stimulus was a slow secretion of 15-20 c.cm. of thick mucoid white fluid, strongly alkaline, which I regard as pancreatic in origin. Four of these five patients showed a curiously similar clinical picture. Three were female and one male. All were very neurotic and all complained of long-standing upper abdominal discomfort, with attacks of severe pain amounting to true colic, coming on two or three hours after food. Three of them were woken about 2 A.M. with severe pain, and all stated that they could not eat eggs or fat without discomfort or pain. In two cases the symptoms had followed a severe mental shock. Only three of these patients were radiographed after administration of tetraiodophenolphthalein by mouth and of these two showed no shadow of the dye ; the third gave a normal concentration. One of the patients showing no dye shadow was operated upon later and the report was " enlarged gall-bladder ; no stones; no inflammatory changes. Cystic duct constricted. Cholecystectomy performed." In this patient an eight-hour residue in the stomach was also shown by barium meal, without any evidence of any organic was no
lesion. I think that these five patients almost certainly belong to the group of functional spastic dyskinesias of the
due to in and the absence of obstructive causes, jaundice complete failure to obtain any bile is suggestive of such functional disorder of the biliary
gall-bladder (Westphal, Newman),
nervous
passages. TABLE III.-Concentrated " B " Bile
"
"
B normal concentrated bile. This is a highly characteristic finding in liver disease, and I have noted it in 7 cases of cirrhosis of the liver (4 of which were proved by operation). Such a combination is likely when the liver is so diseased that it fails to pick out a
TABLE IV.-Oral
Cholecystography
and
Biliary
Drainage
* 8 cases : 1 cholecystitis (oper.), 3 cholecystitis (7), 3 migraine, 1 normal. t 8 cases : 7 cirrhosis of liver, 1 migraine.
the opaque
dye from the portal circulation in sufficient concentration, whereas biliary concentration in the gall-bladder (being healthy) is unimpaired so that dark " B bile is obtained by drainage. The use of "
the two methods in combination may therefore be worth while where cirrhosis of the liver is suspected.
A further characteristic feature of severe cirrhosis of the liver is the striking appearance of the bile which has a bright red colour, unlike the normal yellow, brown, or dark mahogany tinge. As regards the chemical, microscopic, and bacteriological findings in bile, I only propose to mention two points. The first refers to the significance of crystals on microscopic examination, since some writers have regarded the findings of both cholesterol and pigment deposits together as pathognomonic of gall-stones (Bochus). Thus Piersol records that all his cases in which both crystals were found proved to have calculi ; of 40 patients investigated by R4sky, in whom both types of crystals were found in the bile, only 1 showed no calculi or cholecystitis at operation. The observation is one of considerable diagnostic importance, but there are a few records of the incidence of these crystals in the bile of normal
people.
Table V. shows the microscopic findings in my patients, in all of whom the bile was examined soon after withdrawal-just as urine must be examined if TABLE
"
V.-Crystalline Deposits
in Bile
(91 Oases)
"
Failure to withdraw any concentrated B bile, which comes at least in part from the gall-bladder itself, has very much less significance however (again in the absence of obstructive jaundice). From Table III. it will be seen that in over 10 per cent. of normal subjects no gall-bladder (or " B " bile) was found. In none of 10 patients subjected to biliary drainage at periods from 3 months to 14 years after cholecystectomy was any true concentrated " B" bile obtained, though certain workers state that it may be recovered in a proportion of such
patients (Martin). In only about a quarter disease have I obtained " B " bile.
of the a
cases of gall-bladder normally concentrated
when " B " bile is not obtained, the cholecystographic shadow is below normal; but there is a divergence of some 30-40 per cent. in my cases both in patients showing a normal shadow and those giving no shadow or an abnormally faint one. (Table IV.). The second group shows the diagnostic significance of a positive cholecystogram (absent or very faint shadow) combined with the withdrawal of As
a
rule,
is to be attached to crystalline deposits. In 9 out of 43 (21 per cent.) of my presumed normal subjects both types of crystals were present ; they were also found in 10 out of 13 cases of proved gallstones. (I have not attempted any quantitative comparison of the numbers of crystals.) From this it seems that the coexistence of cholesterol and
significance
610
DR. B. J. BOULTON : AGRANULOCYTIC ANGINA
calcium bilirubinate crystals cannot be regarded as pathognomonic of gall-stones, though strongly suggestive of that condition. It is significant that the proportion of cases showing both types of crystals was about the same after cholecystectomy (almost always for gall-stones) as in subjects of cholelithiasis which implies that there is some underlying abnormality of the bile in gall-stone subjects, apart from inflammatory changes in the gall-bladder itself. The last point concerns the significance of protein in the bile, as tested by the very rough Esbach’s estimation. I have found 0’5 part per 1000 represents an empirical normal level, and that the level is increased in more than half the cases of cirrhosis and other diseases of the liver, and also in about the same proportion of cases of gall-bladder disease. It appears that a marked increase of albumin in the bile may be due either to alteration in the secretion of bile by the liver, or to its concentration by the gallbladder. In a number of migraine patients showing a dense shadow by cholecystography-which means that the concentration of gall-bladder bile is increased -the protein content of the bile was particularly
high. I do not think the protein content of the bile is of practical value in the diagnosis of gall-stones or cholelithiasis. In all cases the figures refer to the protein estimated in the most concentrated specimens of bile obtained in each case, though there is usually little difference in this respect between the various fractions of bile removed. SUMMARY
(1) Observations upon biliary drainage in over 100 cases, using magnesium sulphate as a stimulus, are recorded. (2) The rate and volume of biliary flow gave no indication as to the condition of the liver, gall-bladder, or biliary passages. (3) Pain, nausea, and other symptoms were observed during the flow of bile in 16 per cent. of normal subjects, but more frequently in the presence of gall-bladder disease. (4) Failure to obtain any bile by drainage, in the absence of jaundice, was rare (5 cases only) ; dyskinesia of the gall-bladder is suggested as a cause in some of these patients. (5) In 10 per cent. of normal subjects and 75 per cent. of cases of gallbladder disease (6) Results are
no
" B " bile could be withdrawn.
compared between oral cholecystography and biliary drainage in 45 cases ; failure to visualise the gall-bladder by oral cholecystography, in association with the finding of " B " bile by drainage, was found to be characteristic of liver disease. (7) Calcium bilirubinate (pigment) and cholesterol crystals were found together in the bile in 21 of normal subjects and 77 per cent. of gall-stone subjects. My thanks are due to the trustees of the MackenzieMackinnon Research fellowship ; also to Dr. H. Orton and Dr. Courtenay Gage for very kindly carrying out the
radiographic examinations, and to St. Mary’s Hospital for allowing patients under their care.
my me
colleagues at investigate
to
REFERENCES
Bockus, H. L., Shay, H., Willard, J., and Pessel, J. F. : Jour. Amer. Med. Assoc., 1931, xcvi., 312. Chiray, M., and Lebon, J.: Le Tubage Duodenal, Paris, 1924.
Einhorn, M. : The Duodenal Tube, Philadelphia, 1926. Martin, L. : Arch. Internal Med., 1927, xxxix., 356. Newman, C. : THE LANCET, 1933, i., 785. Piersol, G. M., Bockus, H. L., and Shay, H. : Amer. Jour. Med. Sci., 1928, clxxv., 84. Rafsky, H. A. : Amer. Jour. Med. Sci., 1933, clxxxv., 851. Schemensky, W.: Deut. med. Woch., 1926, lii., 2155. Westphal, K., Gleichmann, F., and Mann, W.: Gallenwegsfunktion und Gallensteinleiden, Berlin, 1931.
A CASE OF AGRANULOGYTIC ANGINA
BY B. J.
BOULTON, M.B. Brist.
ASSISTANT RESIDENT MEDICAL OFFICER, HAM GREEN HOSPITAL AND SANATORIUM, BRISTOL
A WOMAN aged 47, unmarried, was admitted to Ham Green Isolation Hospital (Bristol Public Health Department) on May 24th, 1935, the case being
notified
as one
of
suspected faucial diphtheria.
History of illness.-She first consulted her doctor on April 2nd, 1935, complaining of a sore-throat which developed by the 5th into a definite follicular tonsillitis. Swabs taken were returned negative. The throat condition did not clear up until April 14th. On May 21st there was a recurrence rather worse than the previous attack, which rapidly became more severe. On May 23rd an area of inflammation appeared on the dorsum of the left hand. On admission (May 24th) the general condition was poor and the patient appeared to be acutely ill. The temperature was 103° F., the pulse-rate 128, and the respirations 28. Tongue furred. The fauces showed yellow semimembranous sloughs with very little inflammatory reaction apart from narrow areas of erythema around each. Heart sounds poor, lungs normal; the spleen was not palpable and there was no jaundice. The urine contained a trace of albumin. The lower part of the nose was inflamed and swollen, and the dorsum of the left hand and lower
forearm showed a large inflamed area with a blackish superficial necrosis and no attempt at pus formation. The surrounding tissues were soft. Antistreptococcal serum (20 c.cm.) together with antidiphtheritic serum (800 units) was administered intramuscularly. Progress.-By the following day (May 25th) there was no improvement in the patient’s condition and the possibility of this being a case of agranulocytic angina was discussed. A leucocyte count gave a figure of 625 per c.mm. Examination of blood films revealed an obvious neutropenia ; some of the smears showed less than a dozen white cells in all and these were chiefly lymphocytes. A differential count, based on 50 cells only, resulted as follows :6 % Polynuclears 6 % Transitionals Small lymphocytes .. 66 % 0% Eosinophils 0% Large lymphocytes.. 22 ....
....
Arneth count
%IBasophils
....
....
Red cells appear normal.
impossible.
As supplies of pentose nucleotide were not immediately available, sodium nucleinate in doses of gr. were
intramuscularly at four-hourly intervals. (after 12 doses of sodium nucleinate) the leucocyte count gave a figure of 2813 per c.mm.
administered On May 27th
total and the differential count was as follows 51% I Eosinophils Polynuclears Small lymphocytes ..16’5% Large lymphooytes .. 23’0 % Myelocytes ....
Transitionals
....
..
....
Basophils
0%
.... 0% ....
6’0 %
3’5 % I
Class1
Arneth count
:-
1’1
2
..
Arneth index 93’5% Red cells show early ansenua.
..
7% 3
..
4..5 1% 5
Several normoblasts
seen.
These results, however, did not appear to coincide with any improvement in the general condition of the patient who rapidly became worse and died on May 28th. Pentose nucleotide injections in 10 c.cm. doses had been commenced on
the
previous day. Unfortunately,
to carry out
a
it
was
not
possible
post-mortem examination.
unable to obtain any evidence in this of amidopyrin as an exciting cause. There was, however, an obvious focal infection of dental origin. It is doubtful if an earlier administration of pentose nucleotide would have affected the ultimate issue of an acute fulminating case such as this, with a total leucocyte count below 1000.
We
case
are
of
a
previous ingestion
I am indebted to Prof. I. Walker Hall for the blood counts and examination of the films.