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AMMONIA PRODUCTION IN UPPER INTESTINE
388 of vitamin D needed to prevent make a safe guess.
deficiency either
was
was
we can
I believe that
a
of calcium, and how much of deficiency. We do not know, but or
comprehensive
series of tests
to
detect all
early abnormalities after gastrectomy would be complicated and
possibly misleading. Since so many patients are at risk it seems safer to advise Dr. Clayton-Jones that prophylaxis should not be attempted in all, and that not " a grand periodic blunderbuss shot " but small regular supplements should be given. I have suggested 13 daily oral supplements, including an iron salt 300 mg., vitamin B12 500 µg., folic acid 500 µg., vitamin D 500 i.u., and a calcium salt 500 µg., and I proposed that a tablet of this composition should be manufactured. I am pleased to report that progress has already been made by at least
one
drug firm.
Nutritional and Intestinal Unit. The General Hospital, Birmingham 4.
J. ALEXANDER WILLIAMS.
AMMONIA PRODUCTION IN UPPER INTESTINE SIR--There is general agreement that most of the ammonia that bypasses the liver and increases in the blood of patients with cirrhosis is produced by bacterial action on proteins within the large intestine .14 15 In more than half of patients with cirrhosis and low protein tolerance with or without chronic portal-systemic encephalopathy, however, the response to a test-meal of 100 g. of meat shows an increase of arterial ammonia whch reaches a first peak 2 hours after the test-meal;
Increase in arterial ammonia in response to test-meal of 100 g. meat in majority of patients with cirrhosis and low protein tolerance, and effect of antibiotic treatment.
second peak is reached between the 6th and 10th hours, after intermediate decrease (see accompanying figure); both peaks are strikingly reduced by antibiotic treatment. In our opinion, the first peak of arterial-ammonia increase is too early to be ascribed to ammonia production in the large intestine; in none of the patients, indeed, did a-barium meal reach the caecum before 4-6 hours. We therefore consider these findings as evidence of ammonia production by bacterial colonisation of the upper intestine and perhaps of the stomach. Surgical exclusion of the colon has been found useful in patients with fairly good liver function and severe portalsystemic encephalopathy not responsive to diet and medical treatment.14-19Even if some ammonia is still produced in the small intestine of these patients, the effectiveness of the surgical procedure can be explained by the striking decrease of production of ammonia and other toxic substance owing to the exclusion of the colon and the speeded transit through the 13. Williams, J. A. Lancet, 1965, ii, 1128. 14. McDermott, W. V., Victor, M., Point, W. W. New Engl. J. Med. 1962, a
an
15. 16. 17. 18. 19.
267, 850. Walker, J. G., Emlyn-Williams, A., Graigie, A., Rosenoer, V. M., Agnew, J., Sherlock, S. Lancet, 1965, ii, 861. Atkinson, M., Goligher, J. C. ibid. 1960. i, 461. Dienst, S. G. New Engl. J. Med. 1964, 270, 555. Johnston, G. W., Rodgers, H. W. Quoted by Walker et al. (footnote 15). Leger, L., Fourestier, M., Détrie, P., Neveux, J. Y. Presse méd. 1963, 71, 2181.
bowe1.15 It is possible, however, that surgical interventiot may be ineffective in some patients in whom a particularl, large proportion of ammonia is produced in the small intestine FRANCO GIGLIO General Medical Clinic, PAGLIARO LUIGI Palermo University, SALVATORE LE MOLI. Italy.
MEASURING GASTROINTESTINAL PROTEIN LOSS SIR Dr. Moghadam (July 23) claims that 51Cr-labelleè albumin (5lCr A.) is more reliable than 59Fe-labelled iron. dextran (59Fe I.D.) for demonstrating abnormal gastrointestinai protein loss. This may be so, but not for the reasons he gives. In patients with iron-deficiency anaemia Dr. Moghadam assumes that 59Fe I.D. will disappear more rapidly from the circulation than in other patients and thus presumably cause an underestimation of the protein loss. But as early as 1957 it was found that the disappearance-rate of 59Fe J.D. is not increased in iron-deficiency anæmia.1 This objection to the 59Fe I.D. test, therefore, is probably not valid. Anyway, as pointed out by Dr. van Tongeren (July 16), 59Fe J.D. is not suitable for quantitative measurements of gastrointestinal protein loss, which we, of course, do not claim. Neither is 51Cr A. Dr. Moghadam, furthermore, points out that 59Fe I.D. will give incorrect information in patients suffering from gastrointestinal bleeding, because red cells may be labelled with 59Fe. This was not the case in a brief study. During the four days of a 59Fe I.D. test only a small proportion of the injected dose was incorporated in the red cells.2 Thus both objections raised by Dr. Moghadam against the use of 59Fe I.D. are not relevant. We do not claim that 59Fe I.D. is a better substance for detecting gastrointestinal protein loss than is 51Cr A. The results of the two methods seem to be comparable.3 5’Fe l.D. has the advantage that contamination of fasces with urinary activity cannot occur, because no activity is excreted in the urine. We thank Dr. van Tongeren (July 16) for the information about a possible shift of 51 Cr from albumin to transferrin. Itwould be interesting to use 5lCr-labelled transferrin for demonstrating gastrointestinal protein loss. As for our suggestion that the low excretion of "Cr in the faeces after intravenous injection of 5’Cr A. may be due to phagocytosis during passage through the mucosal wall of the gut, this has some slight experiment:) support. Wetterfors4 found in irrigation experiments with dog intestines that "Cr A. passes more slowly from the blood to the lumen of the gut than does 131I-labelled albumin. Of course, other explanations than phagocytosis by reticuloendothelial cells might account for this finding. Department of Clinical Physiology, Glostrup Hospital, and S. B. ANDERSEN Medical Department P, S. JARNUM. Rigshospitalet, Copenhagen.
CANCER OF STOMACH to the steady fall in the incidence of carcinoma of the stomach in the Unite: States since 1935. This trend poses a fascinating epidemiological problem. There have of course been very many change; in the habits and environment of the United States popuhtioc over these thirty years. Perhaps it would be worth speculating about these. Is it possible that the increasing use of deep freeze " for food storage may be important ? Does deep freezing impair hypothetical carcinogenic factors which may be present in certain foods ?
SIR You refer in your annotation (July 16)
"
Cardiac Department, St. Vincent’s Hospital, St. Stephen’s Green, RISTEARD MULCAHY. Dublin 2. 1. Grimes, A. J., Hutt, M. S. R. Br. med. J. 1957, ii, 1074. 2. Garrby, L., Sjölin, S. Acta. med. scand. 1957, 157, 319. 3. Andersen, S. B., Jarnum, S. Lancet, 1966, i, 1060. 4. Wetterfors, J. Acta med. scand. 1965, suppl. 430, p. 1.
deficiency either
was
was
we can
I believe that
a
of calcium, and how much of deficiency. We do not know, but or
comprehensive
series of tests
to
detect all
early abnormalities after gastrectomy would be complicated and
possibly misleading. Since so many patients are at risk it seems safer to advise Dr. Clayton-Jones that prophylaxis should not be attempted in all, and that not " a grand periodic blunderbuss shot " but small regular supplements should be given. I have suggested 13 daily oral supplements, including an iron salt 300 mg., vitamin B12 500 µg., folic acid 500 µg., vitamin D 500 i.u., and a calcium salt 500 µg., and I proposed that a tablet of this composition should be manufactured. I am pleased to report that progress has already been made by at least
one
drug firm.
Nutritional and Intestinal Unit. The General Hospital, Birmingham 4.
J. ALEXANDER WILLIAMS.
AMMONIA PRODUCTION IN UPPER INTESTINE SIR--There is general agreement that most of the ammonia that bypasses the liver and increases in the blood of patients with cirrhosis is produced by bacterial action on proteins within the large intestine .14 15 In more than half of patients with cirrhosis and low protein tolerance with or without chronic portal-systemic encephalopathy, however, the response to a test-meal of 100 g. of meat shows an increase of arterial ammonia whch reaches a first peak 2 hours after the test-meal;
Increase in arterial ammonia in response to test-meal of 100 g. meat in majority of patients with cirrhosis and low protein tolerance, and effect of antibiotic treatment.
second peak is reached between the 6th and 10th hours, after intermediate decrease (see accompanying figure); both peaks are strikingly reduced by antibiotic treatment. In our opinion, the first peak of arterial-ammonia increase is too early to be ascribed to ammonia production in the large intestine; in none of the patients, indeed, did a-barium meal reach the caecum before 4-6 hours. We therefore consider these findings as evidence of ammonia production by bacterial colonisation of the upper intestine and perhaps of the stomach. Surgical exclusion of the colon has been found useful in patients with fairly good liver function and severe portalsystemic encephalopathy not responsive to diet and medical treatment.14-19Even if some ammonia is still produced in the small intestine of these patients, the effectiveness of the surgical procedure can be explained by the striking decrease of production of ammonia and other toxic substance owing to the exclusion of the colon and the speeded transit through the 13. Williams, J. A. Lancet, 1965, ii, 1128. 14. McDermott, W. V., Victor, M., Point, W. W. New Engl. J. Med. 1962, a
an
15. 16. 17. 18. 19.
267, 850. Walker, J. G., Emlyn-Williams, A., Graigie, A., Rosenoer, V. M., Agnew, J., Sherlock, S. Lancet, 1965, ii, 861. Atkinson, M., Goligher, J. C. ibid. 1960. i, 461. Dienst, S. G. New Engl. J. Med. 1964, 270, 555. Johnston, G. W., Rodgers, H. W. Quoted by Walker et al. (footnote 15). Leger, L., Fourestier, M., Détrie, P., Neveux, J. Y. Presse méd. 1963, 71, 2181.
bowe1.15 It is possible, however, that surgical interventiot may be ineffective in some patients in whom a particularl, large proportion of ammonia is produced in the small intestine FRANCO GIGLIO General Medical Clinic, PAGLIARO LUIGI Palermo University, SALVATORE LE MOLI. Italy.
MEASURING GASTROINTESTINAL PROTEIN LOSS SIR Dr. Moghadam (July 23) claims that 51Cr-labelleè albumin (5lCr A.) is more reliable than 59Fe-labelled iron. dextran (59Fe I.D.) for demonstrating abnormal gastrointestinai protein loss. This may be so, but not for the reasons he gives. In patients with iron-deficiency anaemia Dr. Moghadam assumes that 59Fe I.D. will disappear more rapidly from the circulation than in other patients and thus presumably cause an underestimation of the protein loss. But as early as 1957 it was found that the disappearance-rate of 59Fe J.D. is not increased in iron-deficiency anæmia.1 This objection to the 59Fe I.D. test, therefore, is probably not valid. Anyway, as pointed out by Dr. van Tongeren (July 16), 59Fe J.D. is not suitable for quantitative measurements of gastrointestinal protein loss, which we, of course, do not claim. Neither is 51Cr A. Dr. Moghadam, furthermore, points out that 59Fe I.D. will give incorrect information in patients suffering from gastrointestinal bleeding, because red cells may be labelled with 59Fe. This was not the case in a brief study. During the four days of a 59Fe I.D. test only a small proportion of the injected dose was incorporated in the red cells.2 Thus both objections raised by Dr. Moghadam against the use of 59Fe I.D. are not relevant. We do not claim that 59Fe I.D. is a better substance for detecting gastrointestinal protein loss than is 51Cr A. The results of the two methods seem to be comparable.3 5’Fe l.D. has the advantage that contamination of fasces with urinary activity cannot occur, because no activity is excreted in the urine. We thank Dr. van Tongeren (July 16) for the information about a possible shift of 51 Cr from albumin to transferrin. Itwould be interesting to use 5lCr-labelled transferrin for demonstrating gastrointestinal protein loss. As for our suggestion that the low excretion of "Cr in the faeces after intravenous injection of 5’Cr A. may be due to phagocytosis during passage through the mucosal wall of the gut, this has some slight experiment:) support. Wetterfors4 found in irrigation experiments with dog intestines that "Cr A. passes more slowly from the blood to the lumen of the gut than does 131I-labelled albumin. Of course, other explanations than phagocytosis by reticuloendothelial cells might account for this finding. Department of Clinical Physiology, Glostrup Hospital, and S. B. ANDERSEN Medical Department P, S. JARNUM. Rigshospitalet, Copenhagen.
CANCER OF STOMACH to the steady fall in the incidence of carcinoma of the stomach in the Unite: States since 1935. This trend poses a fascinating epidemiological problem. There have of course been very many change; in the habits and environment of the United States popuhtioc over these thirty years. Perhaps it would be worth speculating about these. Is it possible that the increasing use of deep freeze " for food storage may be important ? Does deep freezing impair hypothetical carcinogenic factors which may be present in certain foods ?
SIR You refer in your annotation (July 16)
"
Cardiac Department, St. Vincent’s Hospital, St. Stephen’s Green, RISTEARD MULCAHY. Dublin 2. 1. Grimes, A. J., Hutt, M. S. R. Br. med. J. 1957, ii, 1074. 2. Garrby, L., Sjölin, S. Acta. med. scand. 1957, 157, 319. 3. Andersen, S. B., Jarnum, S. Lancet, 1966, i, 1060. 4. Wetterfors, J. Acta med. scand. 1965, suppl. 430, p. 1.