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THE ASSOCIATION OF CLINICAL PATHOLOGISTS
78 he became
cyanosed ; the cardiac condition was fairly An hour afterwards the cyanosis was more marked ; the pulse was thready and - intermittent. He died at 3.40 P.M. that day. The organs removed at the postmortem showed widespread fat emboli in the capillaries. There was a T-shaped fracture of the patella. Clinically this was a case of the pulmonary type of fat good.
.embolism. There have
been
many
reported
cases
of fat
- embolism
following orthopaedic procedures, the liability to embolism being probably due to the atrophied bones containing more fat than normally. Usually it has followed injuries of, or operations on, the lower extremity. Diagnosis during life is of importance in that treatment can be tried. Wrightstates that "fat embolism should be considered in any case where there are grave or unusual symptoms following trauma whether the trauma be fracture, contusion, concussion, intravenous therapy, delivery, or operation " ! Warthin2 in his excellent and most complete communication on the subject gives eight points in the
diagnosis
:-
1. Injury to bone-marrow or adipose tissue. 2. A cardiac, pulmonary, or cerebral complex or these combined. (Restlessness, stupor, coma, dyspncea, cough.) 3. Free fat-droplets in sputum : fat containing alveolar cells in sputum.
’ Warthin, A. S. : Internat. Clinic, 1913, iv., 171.
4. Free fat-droplets in urine. 5. Examination of eye-grounds for evidence of fat in circulating blood. 6. Examination of venous blood for fat-droplets. 7. Increase of temperature, rather than a lowered
temperature.
8. Examination of skin for
petechial haemorrhages. Warthin regards the presence of fat in the sputum as a
the
important and early sign, fat occurring in
most
sputum before the urine.
Prophylactic measures have been advocated, such the routine employment, and the slow removal, of tourniquets after operations on the limbs likely to give rise to embolism, the incision of tense hsematomata, and even the drainage of blood from the saphenous or femoral vein by cannula on removal of the tourniquet. Treatments employed for an established fat embolism include the injection of 2 per cent. sodium as
carbonate
(formation of a soluble soap), venesection, injection large quantities of saline solution subcutaneously or intravenously, drainage of the thoracic duct, the application of a tourniquet and opening up the operation wound. of
I have to thank Mr. G. H. Colt for permission to publish the first case and Dr. J. Gray for his report on the post-mortem findings, also my thanks are due to Dr. G. S. Banks for the notes of the second case.
MEDICAL SOCIETIES THE ASSOCIATION OF CLINICAL PATHOLOGISTS
meeting was held in the Pathological of Ancoats Hospital, Manchester, with Dr. ARNOLD RENSHAW in the chair, when a discussion was held on The Anaemias Dr. A. F. S. SLADDEN and Dr. AGNES BODOANO (Swansea).communicated observations on the THE
summer
Department
LEUCOCYTE COUNT IN PERNICIOUS ANAEMIA
said that the typical pernicious anaemia patient has either a leucopenia or at least a count near the lower end of the normal range ; further, the polymorph - cells tend to form a relatively lower proportion of .all leucocytes than in normal blood. Cooke and Ponder had shown that the blood in pernicious .anaemia had a relative excess of multilobed polynuclears, so that the weighted mean of lobe content .per cell is increased. Observations based on 220 - counts made on 160 patients by Dr. Sladden and Dr. Bodoano did not warrant the assumption that the seised mean lobe count is peculiar to pernicious anaemia and permanent ; they indicated, however, that such a count is very common in pernicious -an2emia and may thus help in early diagnosis, though it may also occur in microcytic anaemia. When an intercurrent infection occurs the excess of multilobed polynuclears is masked by the outpouring of immature cells. The mean value in polymorph lobes was found to be fairly constant for .any one patient unless infection intervenes ; a raised mean might therefore be found even during a remission of the disease, and this fact was occasionally of value in the diagnosis of what might be termed latent pernicious anaemia. The other aspect of leucocytes in pernicious anaemia to which they desired to draw attention was the characteristic leucopenia.
They
examined did not warrant definite but conclusions, suggested the possibility of drawing a distinction between the course of the polymorph curve and the lymphocyte curve during the progress of a pernicious anaemia which might have value not only for prognosis and the control of treatment, but possibly also as a method of analysing the problems of cell-genesis in the bone-marrow or elsewhere. Dr. Sladden and Dr. Bodoano found the absolute count of lymphocytes to show a rise preceding the rise in the red cells as the result of liver treatment, and a fall preceding the fall of the red cells in relapse. Dr. C. J. YOUNG (Bradford) read a paper on the Polymorphs in Pernicious Anaemia. From observations on the lobation of the polymorphs he concluded that there is both a diminished production of polymorphs and retardation in their removal from the circulation. The number of lobes per 100 cells was raised, attaining a figure in the neighbourhood of 317. This was characteristic of pernicious ansemia. but the same state of affairs might be met with after haemorrhage and after infection. Only by means of absolute lobe counts could it be ascertained whether it was due to diminished production or retarded removal of polymorphs from the circulation. In sepsis occurring in the course of pernicious anaemia, the output of polymorphs of Arneth classes I. and II. might increase and the mean lobe count fall as low Dr. Young attributed the low polymorph as 2-5. count in pernicious anaemia to the replacement of the myeloblastic by erythroblastic marrow. Dr. G. W. GOODHART (London) asked whether it was justifiable to regard the degree of lobation of the polymorphs as an index of their age.-Dr. C. PRICE-JONES (London) asked what was meant by the age of polymorphs. He suggested that the degree of lobation of the polymorphs was an expression of the amount of work they had done ; there being few polymorphs in the blood in pernicious anaemia The
data
79 those present would have more work to do and would therefore acquire more lobes. Dr. PriceJones commented on the difficulty of avoiding errors due to the personal equation in making lobe counts.Dr. SLADDEN replied that once they had experience of the technique, different workers arrived at closely similar ngures on the same preparation.-Dr. YOUNG pointed out that if degree of lobation is an expression of work, then there should be a marked shift to the right in conditions of leucopenia such as agranulocytosis, which is not the case. Dr. N. H. FAIRLEY
(London)
communicated
some
OBSERVATIONS ON SPRUE
He pointed out that Ashford’s theory of intestinal moniliasis had still many adherents and had done much to cloud the issue. The clinical picture presented febrile morning diarrhoea with pale, bulky, gaseous, acid stools ; there was loss of weight, asthenia, sore tongue, a megalocytic anaemia, and sometimes tetany. The disease might occur in natives as well as in white men in the tropics and subtropics. Attention was usually drawn to the condition before the anaemia had fallen lower than 2,500,000 to The Price-Jones 3,000,000 red cells per c.mm. curve was positive in 34 out of 44 cases observed. Achlorhydria was present in many cases but the gastric hydrochloric acid returned after successful treatment. Observations on the blood-sugar and serum calcium showed a deficiency and the basis of the disease was deficient absorption from the alimentary tract ; this affected the anti-anaemic factor of Castle and thus accounted for the anaemia. Treatment was by substitution of the anti-anaemic factor and by diet ; the diet should be high in protein and low in carbohydrates and fats. Dr. G. J. LANGLEY (Manchester) spoke with regret of the disappearance of the strawberry treatment and commented on the difficulty of drawing conclusions as to the disease from cases observed under nontropical conditions.-Dr. J. G. GREENFIELD (London) drew attention to the fact that in spite of the resemblance of the anaemia of sprue to that of the pernicious type, subacute degeneration of the cord was not seen in sprue.-In answer to Dr. JANET VAUGHAN, Dr. FAIRLEY stated that he had never heard of osteomalacia occurring as a result of sprue even of long-standing.-In answer to Dr. GOODHART, Dr. FAIRLEY stated that 20 per cent. of cases relapsed, but that this occurred mainly in patients living under adverse conditions. Relapse could be avoided by suitable diet low in fats and carbohydrate ; it was advisable to persist with treatment with liver for six months after the blood picture had been restored to normal; once the gastric hydrochloric acid had returned to normal cases rarely relapsed. OTHER COMMUNICATIONS
Dr. J. G. GREENFIELD and Dr. ELIZABETH O’FLYNN on the Relation of Pernicious Anaemia to Subacute Combined Degeneration of the Cord (see p. 62), and Dr. JANET VAUGHAN (London) read a paper on the Treatment of the Anaemias (see p. 63). Dr. PRICE-JONES referred to a case of aplastic ansemia in which there had been temporary improvement under copper therapy. Dr. S. C. DYKE (Wolverhampton), as hon. secretary of the association, reported the results of a questionnaire circulated to members on the diagnosis and treatment of pernicious anaemia. He stated that there was a general consensus of opinion that a firm
diagnosis could not be made without employment of all the following procedures : estimation of hoemoglobin, enumeration of red cells, examination of’ stained film of blood, fractional test-meal, van den Bergh reaction of serum, estimation by some mean& of the mean diameter of the red cells. A positive van den Bergh reaction had been found in the vast majority of cases and except in very few instances. was of the indirect type. There was general agreement that hydrochloric acid therapy was useless in improving the blood picture, but it was of service in combating gastro-alimentary symptoms ; iron was found to be of no avail in the early stages of treatment when the colour-index was high, but it was of value when the red cells had been restored to something approaching a normal level, at which time the colourindex tended to fall. Dr. F. B. SMITH (Preston) demonstrated the halometric device of Merlyn-Price and communicated observations on 85 cases of pernicious ansemia. Contrary to what is generally stated, he found the condition to be more common in women than in men ; he also found that the megalocytosis did not disappear until the haemoglobin had reached over 70 per cent. Dr. DYKE communicated the results of an attempt. to assay the value of preparation of liver forparenteral injection in the treatment of pernicious ansemia by means of the reticulocyte response (see p. 59). In the subsequent discussion various speakers drew attention to the waste of money and material in the prescription of preparations of the anti-ansemic factor to unsuitable cases and in the use of inefficient
preparations. Dr. DYKE pointed out that the waste is not only of money and material, but also of human health and life, and stressed the fact that it is impossible to treat properly any case of pernicious anaemia without frequent examination of the blood.-Dr. JANE’!’ VAUGHAN stated that the same applied to cases of microcytic anaemia on iron therapy. Various members drew attention to the need for concerted action to put into effect the recent advances in the treatment of the anaemias. The following resolution embodying the sense of the meeting was proposed by Dr. GREENFIELD :" That this association is of the opinion that the failure provide laboratory facilities for patients under the National Health Insurance Acts, suffering from or suspected to suffer from anasmia, is responsible for much wastage both of material and of human efficiency and life, and considers that such laboratory service should be made available in recognised centres both for initial differential diagnosis and for the periodical examinations necessary to assure the maintenance of a sound state of health." to
The resolution was seconded by Dr. GOODMAN PLATTS (York) and passed unanimously.
(London) communicated observations
LEICESTER ROYAL for
INFIRMARY.-According to the
6902 in-patients were admitted, which is a small increase. Their average stay was 19-86 days, and the average cost per occupied bed was B152. Deaths within 48 hours of admission numbered 207. There were 14,000 new out-patients, but although this was a fall of 471, there were about 900 more attendances. There were 18,978 casualties, an increase of 1700 ;9338 traffic accidents were admitted to the wards, of which half were motor-car casualties; accidents with motor-cyclescame next with 115. These patients spent 6906 days in hospital and cost JE2886 , 55 of them died, 17 from injuries. received in motor-car accidents.
report
1932,
cyanosed ; the cardiac condition was fairly An hour afterwards the cyanosis was more marked ; the pulse was thready and - intermittent. He died at 3.40 P.M. that day. The organs removed at the postmortem showed widespread fat emboli in the capillaries. There was a T-shaped fracture of the patella. Clinically this was a case of the pulmonary type of fat good.
.embolism. There have
been
many
reported
cases
of fat
- embolism
following orthopaedic procedures, the liability to embolism being probably due to the atrophied bones containing more fat than normally. Usually it has followed injuries of, or operations on, the lower extremity. Diagnosis during life is of importance in that treatment can be tried. Wrightstates that "fat embolism should be considered in any case where there are grave or unusual symptoms following trauma whether the trauma be fracture, contusion, concussion, intravenous therapy, delivery, or operation " ! Warthin2 in his excellent and most complete communication on the subject gives eight points in the
diagnosis
:-
1. Injury to bone-marrow or adipose tissue. 2. A cardiac, pulmonary, or cerebral complex or these combined. (Restlessness, stupor, coma, dyspncea, cough.) 3. Free fat-droplets in sputum : fat containing alveolar cells in sputum.
’ Warthin, A. S. : Internat. Clinic, 1913, iv., 171.
4. Free fat-droplets in urine. 5. Examination of eye-grounds for evidence of fat in circulating blood. 6. Examination of venous blood for fat-droplets. 7. Increase of temperature, rather than a lowered
temperature.
8. Examination of skin for
petechial haemorrhages. Warthin regards the presence of fat in the sputum as a
the
important and early sign, fat occurring in
most
sputum before the urine.
Prophylactic measures have been advocated, such the routine employment, and the slow removal, of tourniquets after operations on the limbs likely to give rise to embolism, the incision of tense hsematomata, and even the drainage of blood from the saphenous or femoral vein by cannula on removal of the tourniquet. Treatments employed for an established fat embolism include the injection of 2 per cent. sodium as
carbonate
(formation of a soluble soap), venesection, injection large quantities of saline solution subcutaneously or intravenously, drainage of the thoracic duct, the application of a tourniquet and opening up the operation wound. of
I have to thank Mr. G. H. Colt for permission to publish the first case and Dr. J. Gray for his report on the post-mortem findings, also my thanks are due to Dr. G. S. Banks for the notes of the second case.
MEDICAL SOCIETIES THE ASSOCIATION OF CLINICAL PATHOLOGISTS
meeting was held in the Pathological of Ancoats Hospital, Manchester, with Dr. ARNOLD RENSHAW in the chair, when a discussion was held on The Anaemias Dr. A. F. S. SLADDEN and Dr. AGNES BODOANO (Swansea).communicated observations on the THE
summer
Department
LEUCOCYTE COUNT IN PERNICIOUS ANAEMIA
said that the typical pernicious anaemia patient has either a leucopenia or at least a count near the lower end of the normal range ; further, the polymorph - cells tend to form a relatively lower proportion of .all leucocytes than in normal blood. Cooke and Ponder had shown that the blood in pernicious .anaemia had a relative excess of multilobed polynuclears, so that the weighted mean of lobe content .per cell is increased. Observations based on 220 - counts made on 160 patients by Dr. Sladden and Dr. Bodoano did not warrant the assumption that the seised mean lobe count is peculiar to pernicious anaemia and permanent ; they indicated, however, that such a count is very common in pernicious -an2emia and may thus help in early diagnosis, though it may also occur in microcytic anaemia. When an intercurrent infection occurs the excess of multilobed polynuclears is masked by the outpouring of immature cells. The mean value in polymorph lobes was found to be fairly constant for .any one patient unless infection intervenes ; a raised mean might therefore be found even during a remission of the disease, and this fact was occasionally of value in the diagnosis of what might be termed latent pernicious anaemia. The other aspect of leucocytes in pernicious anaemia to which they desired to draw attention was the characteristic leucopenia.
They
examined did not warrant definite but conclusions, suggested the possibility of drawing a distinction between the course of the polymorph curve and the lymphocyte curve during the progress of a pernicious anaemia which might have value not only for prognosis and the control of treatment, but possibly also as a method of analysing the problems of cell-genesis in the bone-marrow or elsewhere. Dr. Sladden and Dr. Bodoano found the absolute count of lymphocytes to show a rise preceding the rise in the red cells as the result of liver treatment, and a fall preceding the fall of the red cells in relapse. Dr. C. J. YOUNG (Bradford) read a paper on the Polymorphs in Pernicious Anaemia. From observations on the lobation of the polymorphs he concluded that there is both a diminished production of polymorphs and retardation in their removal from the circulation. The number of lobes per 100 cells was raised, attaining a figure in the neighbourhood of 317. This was characteristic of pernicious ansemia. but the same state of affairs might be met with after haemorrhage and after infection. Only by means of absolute lobe counts could it be ascertained whether it was due to diminished production or retarded removal of polymorphs from the circulation. In sepsis occurring in the course of pernicious anaemia, the output of polymorphs of Arneth classes I. and II. might increase and the mean lobe count fall as low Dr. Young attributed the low polymorph as 2-5. count in pernicious anaemia to the replacement of the myeloblastic by erythroblastic marrow. Dr. G. W. GOODHART (London) asked whether it was justifiable to regard the degree of lobation of the polymorphs as an index of their age.-Dr. C. PRICE-JONES (London) asked what was meant by the age of polymorphs. He suggested that the degree of lobation of the polymorphs was an expression of the amount of work they had done ; there being few polymorphs in the blood in pernicious anaemia The
data
79 those present would have more work to do and would therefore acquire more lobes. Dr. PriceJones commented on the difficulty of avoiding errors due to the personal equation in making lobe counts.Dr. SLADDEN replied that once they had experience of the technique, different workers arrived at closely similar ngures on the same preparation.-Dr. YOUNG pointed out that if degree of lobation is an expression of work, then there should be a marked shift to the right in conditions of leucopenia such as agranulocytosis, which is not the case. Dr. N. H. FAIRLEY
(London)
communicated
some
OBSERVATIONS ON SPRUE
He pointed out that Ashford’s theory of intestinal moniliasis had still many adherents and had done much to cloud the issue. The clinical picture presented febrile morning diarrhoea with pale, bulky, gaseous, acid stools ; there was loss of weight, asthenia, sore tongue, a megalocytic anaemia, and sometimes tetany. The disease might occur in natives as well as in white men in the tropics and subtropics. Attention was usually drawn to the condition before the anaemia had fallen lower than 2,500,000 to The Price-Jones 3,000,000 red cells per c.mm. curve was positive in 34 out of 44 cases observed. Achlorhydria was present in many cases but the gastric hydrochloric acid returned after successful treatment. Observations on the blood-sugar and serum calcium showed a deficiency and the basis of the disease was deficient absorption from the alimentary tract ; this affected the anti-anaemic factor of Castle and thus accounted for the anaemia. Treatment was by substitution of the anti-anaemic factor and by diet ; the diet should be high in protein and low in carbohydrates and fats. Dr. G. J. LANGLEY (Manchester) spoke with regret of the disappearance of the strawberry treatment and commented on the difficulty of drawing conclusions as to the disease from cases observed under nontropical conditions.-Dr. J. G. GREENFIELD (London) drew attention to the fact that in spite of the resemblance of the anaemia of sprue to that of the pernicious type, subacute degeneration of the cord was not seen in sprue.-In answer to Dr. JANET VAUGHAN, Dr. FAIRLEY stated that he had never heard of osteomalacia occurring as a result of sprue even of long-standing.-In answer to Dr. GOODHART, Dr. FAIRLEY stated that 20 per cent. of cases relapsed, but that this occurred mainly in patients living under adverse conditions. Relapse could be avoided by suitable diet low in fats and carbohydrate ; it was advisable to persist with treatment with liver for six months after the blood picture had been restored to normal; once the gastric hydrochloric acid had returned to normal cases rarely relapsed. OTHER COMMUNICATIONS
Dr. J. G. GREENFIELD and Dr. ELIZABETH O’FLYNN on the Relation of Pernicious Anaemia to Subacute Combined Degeneration of the Cord (see p. 62), and Dr. JANET VAUGHAN (London) read a paper on the Treatment of the Anaemias (see p. 63). Dr. PRICE-JONES referred to a case of aplastic ansemia in which there had been temporary improvement under copper therapy. Dr. S. C. DYKE (Wolverhampton), as hon. secretary of the association, reported the results of a questionnaire circulated to members on the diagnosis and treatment of pernicious anaemia. He stated that there was a general consensus of opinion that a firm
diagnosis could not be made without employment of all the following procedures : estimation of hoemoglobin, enumeration of red cells, examination of’ stained film of blood, fractional test-meal, van den Bergh reaction of serum, estimation by some mean& of the mean diameter of the red cells. A positive van den Bergh reaction had been found in the vast majority of cases and except in very few instances. was of the indirect type. There was general agreement that hydrochloric acid therapy was useless in improving the blood picture, but it was of service in combating gastro-alimentary symptoms ; iron was found to be of no avail in the early stages of treatment when the colour-index was high, but it was of value when the red cells had been restored to something approaching a normal level, at which time the colourindex tended to fall. Dr. F. B. SMITH (Preston) demonstrated the halometric device of Merlyn-Price and communicated observations on 85 cases of pernicious ansemia. Contrary to what is generally stated, he found the condition to be more common in women than in men ; he also found that the megalocytosis did not disappear until the haemoglobin had reached over 70 per cent. Dr. DYKE communicated the results of an attempt. to assay the value of preparation of liver forparenteral injection in the treatment of pernicious ansemia by means of the reticulocyte response (see p. 59). In the subsequent discussion various speakers drew attention to the waste of money and material in the prescription of preparations of the anti-ansemic factor to unsuitable cases and in the use of inefficient
preparations. Dr. DYKE pointed out that the waste is not only of money and material, but also of human health and life, and stressed the fact that it is impossible to treat properly any case of pernicious anaemia without frequent examination of the blood.-Dr. JANE’!’ VAUGHAN stated that the same applied to cases of microcytic anaemia on iron therapy. Various members drew attention to the need for concerted action to put into effect the recent advances in the treatment of the anaemias. The following resolution embodying the sense of the meeting was proposed by Dr. GREENFIELD :" That this association is of the opinion that the failure provide laboratory facilities for patients under the National Health Insurance Acts, suffering from or suspected to suffer from anasmia, is responsible for much wastage both of material and of human efficiency and life, and considers that such laboratory service should be made available in recognised centres both for initial differential diagnosis and for the periodical examinations necessary to assure the maintenance of a sound state of health." to
The resolution was seconded by Dr. GOODMAN PLATTS (York) and passed unanimously.
(London) communicated observations
LEICESTER ROYAL for
INFIRMARY.-According to the
6902 in-patients were admitted, which is a small increase. Their average stay was 19-86 days, and the average cost per occupied bed was B152. Deaths within 48 hours of admission numbered 207. There were 14,000 new out-patients, but although this was a fall of 471, there were about 900 more attendances. There were 18,978 casualties, an increase of 1700 ;9338 traffic accidents were admitted to the wards, of which half were motor-car casualties; accidents with motor-cyclescame next with 115. These patients spent 6906 days in hospital and cost JE2886 , 55 of them died, 17 from injuries. received in motor-car accidents.
report
1932,