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THE ABORTING TYPE OF PERFORATED PEPTIC ULCER
THE ÆTIOLOGY OF MEGALOCYTIC ANAEMIAS
16,
starvation to produce experimental megalocytic anaemia in animals. B. C. GUHA and L. W. M’APSONalready claim to have. produced an anaemia in rats by deficiency of vitamin B2, but do not state whether it was megalocytic. B. SuRE, M. C. KiK, and D. J. WA.LKER,23 however, fail to substantiate these findings. Secondly, STRAUSS and CASTLE suggest that since vitamin Bl is effective in
1932
THE ÆTIOLOGY OF MEGALOCYTIC ANÆMIAS IT has become evident, in the last year, that the
megalocytic
anaemias
are a more
complex
group
was
found
than’at first appeared probable, when it
135
tions, apart from their elucidation of the mechanism of production of the megalocytic anaemias, lead their authors to advance two interesting hypotheses. In the first place they suggest that it might be possible by means of vitamin B2, or extrinsic factor,
THE LANCET. .LONDON: SATURDAY, JULY
.
that they all responded well to liver treatment. L. WILLS demonstrated in 1931 that tropical megalocytic anaemia was curable by large doses of marmite. J. M. VAUGHAN and D. HUNTER this year showed that such an anaemia, in association with coeliac disease, was also responsive to marmite, while W. B. CASTLE reported to the Association of American Physicians that yeast preparations were effective in sprue. S. DAVIDSON, on the other hand, had conclusively proved that marmite was valueless in Addisonian pernicious anaemia. It was clear, therefore, that a large group of ,megalocytic anaemias differed from Addisonian pernicious anaemia in their response to yeast preparations. In our present issue Dr. M. B. STRAUSS and Dr. W. B. CASTLE describe experiments which attempt to elucidate the meaning of this difference, and in so doing advance our knowledge of the factors essential to hsemopoiesis. W. B. CASTLE and his fellow-workers have previously shown that the effective haemopoietic factor in liver is the result of the interaction of an intrinsic factor present in normal gastric juice, and an extrinsic factor present in animal protein. Their
treating experimental subacute combined system disease in dogs, but’ ineffective in treating the disease in patients, its occurrence in the latter is due to lack of some further intrinsic factor in gastric juice needed for interaction with the extrinsic factor, B2,, in order to produce the effective neurological principle. This attractive suggestion receives support from the fact that those anaemias, dependent upon lack of extrinsic factor only, are rarely, if ever, associated with any of the severe nervous lesions. Whatever the fate of such a theory the work here discussed introduces a valuable new concept of the possible mode of action of vitamins. Deficiency diseases may be due, in some instances, to lack of effective interaction between the essential vitamin and some substance in the gastro-intestinal canal, or even to failure of the internal metabolism, rather than to a defective diet.
THE ABORTING TYPE OF PERFORATED PEPTIC ULCER
IT is well known to surgeons who operate upon present experiments are concerned with the nature of this extrinsic factor, and suggest that it is abdominal emergencies that after the initial probably vitamin B2. By means of feeding experi- devastating onset symptoms of a perforating gastric ments they show that the extrinsic factor is not ulcer, a period of recovery frequently occurs during present in washed casein, in wheat gluten, and in which the clinical signs regress to such a degree -
from animal and vegetable all substances sources, poor or deficient in vitamin the other On hand, it is found in autolysed Ba. a rich source of vitamin B2, in 20 times the yeast, concentration that it is in beefsteak, and can be separated from the yeast protein. The extrinsic factor is not destroyed by autoclaving, which is a ,process fatal to vitamin B3L. Autoclaved yeast treated with normal gastric juice was found to be extremely effective in the treatment of Addisonian pernicious anaemia. STRAUSS and CASTLE suggest, then, as a working hypothesis, that vitamin B2 is the extrinsic factor. The development of a megalocytic type of anaemia may theoretically be dependent upon three mechanisms :— (1) Lack of the intrinsic factor, as in Addisonian
washed
that the diagnosis becomes a matter of doubt. This period of recession is followed later by signs of general peritonitis which make the nature of the illness again clear. It is also recognised that the mortality curve, in relation to the interval which has elapsed between the onset and operation, after running parallel with the base line for about six hours begins to rise rapidly and continues to do so until the 24th hour, after which it falls somewhat to the 30th hour. The explanation of this curious improved outlook in late neglected cases is easy to imagine. The frequency with which the omentum or liver are adherent to the site of a perforation leads us to believe that in such cases leakage has been impeded for some hours. There has, in fact, been a subsequent perforation. Sometimes the anaemia.. of the leak may be permanent, and pernicious (2) Lack of the extrinsic factor, as in sprue, coeliac stoppage spontaneous cure of the perforated ulcer will occur. disease, and tropical anaemia. (3) Failure of absorption of the effective principle, Most surgeons can recall isolated instances where an acute abdominal catastrophe which has rapidly as in certain cases resistant to oral administration.
nucleo-protein
It must be remembered, however, that CASTLE 1 Guha, B. C., and Mapson, L. W.: Biochem. Jour., 1931, has demonstrated the lack of intrinsic factor in xxv., 1673. 2 Sure, B., Kik, M. C., and Walker, D. J.: Jour. Biol. Chem. certain cases of sprue and therefore, if yeast fails in 1929, lxxxiii., 387. 3 Sure, B., and Kik, M. C.: Proc. Soc. Exp. Biol., N.Y., 1931. - treatment, liver should be given. These observa-, xxviii., 496.
136
passed off, but where a subsequent operation done can be determined with a reasonable degree of usually under the belief that the attack was one of certainty that the perforation is securely sealed and biliary colic, has revealed a perforation of a gastric the peritonitis is limited and receding." How this or duodenal ulcer which has been sealed by an forecast is to be made is not propounded, and in adhesion of the liver, omentum, or gall-bladder to view of the active solvent action of gastric juice on the ulcer site. It is not, however, recognised that fibrin, which at this stage is the occluding substance, this may be a fairly common phenomenon. H. A. it is open to doubt whether it is wise to counsel a SINGEB and R. T. VAUGHANdraw attention to a non-operative treatment at this stage. Even if a number of such cases, and suggest that many of less conservative policy proves desirable, practi. them never come under the observation of the tioners and surgeons will be glad to have had their surgeon since the acute symptoms are quite attention directed to the frequency of spontaneous transient in nature. a forme-fruste cure of a gastric perforation or aborted of ulcer. This In every case there is a very severe attack of phenomenon type abdominal pain, so intense that the patient is evidently occurs much more often than has been literally struck down. He ’collapses on the floor, hitherto suspected and may account for the perhaps may be able to drag himself home, and undramatic end of an attack so transient that its always has the sense of some very grave and gravity is hardly believed by those who have not possibly mortal disturbance in his abdomen, so that witnessed it. his medical adviser is summoned. By the time of THE LISTER INSTITUTE the latter’s arrival, the acute pain and sense of distress may have all passed off, so the perplexed THE annual report of the governing body of doctor, of necessity, diagnoses a biliary or intestinal the Lister Institute, presented to the council and colic. Should he arrive during the acute stage, the members at their meeting on May 25th, makes tenderness and intense rigidity lead him to send interesting reading. In these days of congested the patient to hospital with the diagnosis of perpublication it is an excellent plan for institutes of forated ulcer where, owing to subsidence of the scientific research to send out each year an orderly symptoms, the house surgeon in his turn may be account of what they are doing with just enough perplexed and cast strong doubts upon the practi- detail to show where their several inquiries are; tioner’s clinical acumen. The rapidity with which a good many organisations do so already, and we abdominal signs calling quite distinctly for immehope the number will increase. It is evident from diate intervention to close a perforation disappear the present report that the standards of sound is astonishing. The patient in a very short space work and the atmosphere of genuine research of time feels completely different; his pulse may which Sir CHARLES MARTIN cultivated with such be a little raised (80-90), but his abdominal wall success are, as we should all expect, being amply will be flaccid and nothing will remain but some maintained. Sir CHARLES is in Australia looking tenderness, usually under the right costal margin. after the nutrition of sheep, and we congratulate The condition simulates biliary colic and chole- Prof. J. C. G. LEDINGHAM and his staff on the way cystitis so strongly that an aid to diagnosis, of in which they carry on one of the best traditions which VAUGHAN and SINGER emphasise the value, in Britain. may be well worth the delay and discomfort to the The report is classified by departments, and the it X involves. An at the examination ray patient changing emphasis of bacteriology is shown by flaccid stage may show gas under the right dome the fact that rather more than half of what appears of the diaphragm, particularly if the stomach under that heading deals with viruses. The director contents have been first syphoned off and the and Dr. G. H. EAGLES—so much of the work is patient turned on his left side, so that intragastric collaborative that we must be pardoned if all air may go to the pyloric end where the perforation the names involved are not mentioned-have is likely to be. It is unnecessary to state that the pursued their studies of the virus of vaccinia and movements of the patient and the manipulation of by cultural agglutination and centrifugal experithe syphon tube must be carried out with extreme ments have done much to consolidate their claim gentleness and skill. Examination of the recto- that the Paschen bodies-readily visible particles vesical pouch may reveal tenderness if some -are really the virus itself, though the proposition irritating acid contents of the stomach have fallen that they are strictly analogous to bacteria still to this lowest point of the peritoneal cavity and awaits the demonstration that they multiply by caused an inflammatory reaction. dividing their own substance. In the other The intensity of the primary abdominal pain is direction, suggestions are made that the causative the most significant point in the history. SINGER agent of pleuro-pneumonia is possibly a fungus and VAUGHAN recommend that no operation should rather than something on the boundary between be performed if the patient is first seen only after bacteria and viruses as is commonly supposed. 48 hours, and no signs of diffuse peritonitis are Particularly notable in this section is the work of manifest, and quote a number of cases in support Dr. E. W. HURST, now happily recovering from a of this policy. They recommend surgery in every dangerous illness, on poliomyelitis, and especially case seen during the first 24 hours ; during the on the extraordinary form of rabies which occurs second 24 hours they refrain from operating if " it in Trinidad in men and cattle without involving dogs, the true nature of which was discovered only 1 Surgery, Gynæc., and Obstet., 1930, l., 10; and 1932, liv., ’ by inoculating monkeys at Chelsea. Under bacteria945. -
"
,
"
16,
starvation to produce experimental megalocytic anaemia in animals. B. C. GUHA and L. W. M’APSONalready claim to have. produced an anaemia in rats by deficiency of vitamin B2, but do not state whether it was megalocytic. B. SuRE, M. C. KiK, and D. J. WA.LKER,23 however, fail to substantiate these findings. Secondly, STRAUSS and CASTLE suggest that since vitamin Bl is effective in
1932
THE ÆTIOLOGY OF MEGALOCYTIC ANÆMIAS IT has become evident, in the last year, that the
megalocytic
anaemias
are a more
complex
group
was
found
than’at first appeared probable, when it
135
tions, apart from their elucidation of the mechanism of production of the megalocytic anaemias, lead their authors to advance two interesting hypotheses. In the first place they suggest that it might be possible by means of vitamin B2, or extrinsic factor,
THE LANCET. .LONDON: SATURDAY, JULY
.
that they all responded well to liver treatment. L. WILLS demonstrated in 1931 that tropical megalocytic anaemia was curable by large doses of marmite. J. M. VAUGHAN and D. HUNTER this year showed that such an anaemia, in association with coeliac disease, was also responsive to marmite, while W. B. CASTLE reported to the Association of American Physicians that yeast preparations were effective in sprue. S. DAVIDSON, on the other hand, had conclusively proved that marmite was valueless in Addisonian pernicious anaemia. It was clear, therefore, that a large group of ,megalocytic anaemias differed from Addisonian pernicious anaemia in their response to yeast preparations. In our present issue Dr. M. B. STRAUSS and Dr. W. B. CASTLE describe experiments which attempt to elucidate the meaning of this difference, and in so doing advance our knowledge of the factors essential to hsemopoiesis. W. B. CASTLE and his fellow-workers have previously shown that the effective haemopoietic factor in liver is the result of the interaction of an intrinsic factor present in normal gastric juice, and an extrinsic factor present in animal protein. Their
treating experimental subacute combined system disease in dogs, but’ ineffective in treating the disease in patients, its occurrence in the latter is due to lack of some further intrinsic factor in gastric juice needed for interaction with the extrinsic factor, B2,, in order to produce the effective neurological principle. This attractive suggestion receives support from the fact that those anaemias, dependent upon lack of extrinsic factor only, are rarely, if ever, associated with any of the severe nervous lesions. Whatever the fate of such a theory the work here discussed introduces a valuable new concept of the possible mode of action of vitamins. Deficiency diseases may be due, in some instances, to lack of effective interaction between the essential vitamin and some substance in the gastro-intestinal canal, or even to failure of the internal metabolism, rather than to a defective diet.
THE ABORTING TYPE OF PERFORATED PEPTIC ULCER
IT is well known to surgeons who operate upon present experiments are concerned with the nature of this extrinsic factor, and suggest that it is abdominal emergencies that after the initial probably vitamin B2. By means of feeding experi- devastating onset symptoms of a perforating gastric ments they show that the extrinsic factor is not ulcer, a period of recovery frequently occurs during present in washed casein, in wheat gluten, and in which the clinical signs regress to such a degree -
from animal and vegetable all substances sources, poor or deficient in vitamin the other On hand, it is found in autolysed Ba. a rich source of vitamin B2, in 20 times the yeast, concentration that it is in beefsteak, and can be separated from the yeast protein. The extrinsic factor is not destroyed by autoclaving, which is a ,process fatal to vitamin B3L. Autoclaved yeast treated with normal gastric juice was found to be extremely effective in the treatment of Addisonian pernicious anaemia. STRAUSS and CASTLE suggest, then, as a working hypothesis, that vitamin B2 is the extrinsic factor. The development of a megalocytic type of anaemia may theoretically be dependent upon three mechanisms :— (1) Lack of the intrinsic factor, as in Addisonian
washed
that the diagnosis becomes a matter of doubt. This period of recession is followed later by signs of general peritonitis which make the nature of the illness again clear. It is also recognised that the mortality curve, in relation to the interval which has elapsed between the onset and operation, after running parallel with the base line for about six hours begins to rise rapidly and continues to do so until the 24th hour, after which it falls somewhat to the 30th hour. The explanation of this curious improved outlook in late neglected cases is easy to imagine. The frequency with which the omentum or liver are adherent to the site of a perforation leads us to believe that in such cases leakage has been impeded for some hours. There has, in fact, been a subsequent perforation. Sometimes the anaemia.. of the leak may be permanent, and pernicious (2) Lack of the extrinsic factor, as in sprue, coeliac stoppage spontaneous cure of the perforated ulcer will occur. disease, and tropical anaemia. (3) Failure of absorption of the effective principle, Most surgeons can recall isolated instances where an acute abdominal catastrophe which has rapidly as in certain cases resistant to oral administration.
nucleo-protein
It must be remembered, however, that CASTLE 1 Guha, B. C., and Mapson, L. W.: Biochem. Jour., 1931, has demonstrated the lack of intrinsic factor in xxv., 1673. 2 Sure, B., Kik, M. C., and Walker, D. J.: Jour. Biol. Chem. certain cases of sprue and therefore, if yeast fails in 1929, lxxxiii., 387. 3 Sure, B., and Kik, M. C.: Proc. Soc. Exp. Biol., N.Y., 1931. - treatment, liver should be given. These observa-, xxviii., 496.
136
passed off, but where a subsequent operation done can be determined with a reasonable degree of usually under the belief that the attack was one of certainty that the perforation is securely sealed and biliary colic, has revealed a perforation of a gastric the peritonitis is limited and receding." How this or duodenal ulcer which has been sealed by an forecast is to be made is not propounded, and in adhesion of the liver, omentum, or gall-bladder to view of the active solvent action of gastric juice on the ulcer site. It is not, however, recognised that fibrin, which at this stage is the occluding substance, this may be a fairly common phenomenon. H. A. it is open to doubt whether it is wise to counsel a SINGEB and R. T. VAUGHANdraw attention to a non-operative treatment at this stage. Even if a number of such cases, and suggest that many of less conservative policy proves desirable, practi. them never come under the observation of the tioners and surgeons will be glad to have had their surgeon since the acute symptoms are quite attention directed to the frequency of spontaneous transient in nature. a forme-fruste cure of a gastric perforation or aborted of ulcer. This In every case there is a very severe attack of phenomenon type abdominal pain, so intense that the patient is evidently occurs much more often than has been literally struck down. He ’collapses on the floor, hitherto suspected and may account for the perhaps may be able to drag himself home, and undramatic end of an attack so transient that its always has the sense of some very grave and gravity is hardly believed by those who have not possibly mortal disturbance in his abdomen, so that witnessed it. his medical adviser is summoned. By the time of THE LISTER INSTITUTE the latter’s arrival, the acute pain and sense of distress may have all passed off, so the perplexed THE annual report of the governing body of doctor, of necessity, diagnoses a biliary or intestinal the Lister Institute, presented to the council and colic. Should he arrive during the acute stage, the members at their meeting on May 25th, makes tenderness and intense rigidity lead him to send interesting reading. In these days of congested the patient to hospital with the diagnosis of perpublication it is an excellent plan for institutes of forated ulcer where, owing to subsidence of the scientific research to send out each year an orderly symptoms, the house surgeon in his turn may be account of what they are doing with just enough perplexed and cast strong doubts upon the practi- detail to show where their several inquiries are; tioner’s clinical acumen. The rapidity with which a good many organisations do so already, and we abdominal signs calling quite distinctly for immehope the number will increase. It is evident from diate intervention to close a perforation disappear the present report that the standards of sound is astonishing. The patient in a very short space work and the atmosphere of genuine research of time feels completely different; his pulse may which Sir CHARLES MARTIN cultivated with such be a little raised (80-90), but his abdominal wall success are, as we should all expect, being amply will be flaccid and nothing will remain but some maintained. Sir CHARLES is in Australia looking tenderness, usually under the right costal margin. after the nutrition of sheep, and we congratulate The condition simulates biliary colic and chole- Prof. J. C. G. LEDINGHAM and his staff on the way cystitis so strongly that an aid to diagnosis, of in which they carry on one of the best traditions which VAUGHAN and SINGER emphasise the value, in Britain. may be well worth the delay and discomfort to the The report is classified by departments, and the it X involves. An at the examination ray patient changing emphasis of bacteriology is shown by flaccid stage may show gas under the right dome the fact that rather more than half of what appears of the diaphragm, particularly if the stomach under that heading deals with viruses. The director contents have been first syphoned off and the and Dr. G. H. EAGLES—so much of the work is patient turned on his left side, so that intragastric collaborative that we must be pardoned if all air may go to the pyloric end where the perforation the names involved are not mentioned-have is likely to be. It is unnecessary to state that the pursued their studies of the virus of vaccinia and movements of the patient and the manipulation of by cultural agglutination and centrifugal experithe syphon tube must be carried out with extreme ments have done much to consolidate their claim gentleness and skill. Examination of the recto- that the Paschen bodies-readily visible particles vesical pouch may reveal tenderness if some -are really the virus itself, though the proposition irritating acid contents of the stomach have fallen that they are strictly analogous to bacteria still to this lowest point of the peritoneal cavity and awaits the demonstration that they multiply by caused an inflammatory reaction. dividing their own substance. In the other The intensity of the primary abdominal pain is direction, suggestions are made that the causative the most significant point in the history. SINGER agent of pleuro-pneumonia is possibly a fungus and VAUGHAN recommend that no operation should rather than something on the boundary between be performed if the patient is first seen only after bacteria and viruses as is commonly supposed. 48 hours, and no signs of diffuse peritonitis are Particularly notable in this section is the work of manifest, and quote a number of cases in support Dr. E. W. HURST, now happily recovering from a of this policy. They recommend surgery in every dangerous illness, on poliomyelitis, and especially case seen during the first 24 hours ; during the on the extraordinary form of rabies which occurs second 24 hours they refrain from operating if " it in Trinidad in men and cattle without involving dogs, the true nature of which was discovered only 1 Surgery, Gynæc., and Obstet., 1930, l., 10; and 1932, liv., ’ by inoculating monkeys at Chelsea. Under bacteria945. -
"
,
"