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PREVENTING AIR-EMBOLISM AFTER ABDOMINAL INJURY
1395 ABUSE OF ’FILON’
SIR,-We think it important to describe an unpublicised side-effect of the drug mixture ’Filon ’ (phenmetrazine theoclate 30 mg., phenbutrazate hydrochloride 20 mg.), said to have the same anorectic action as ’Preludin’ (phenmetrazine hydrochloride 25 mg.) but not its addictive properties. We have a new patient, a man of 33, who is without doubt
induction of the refractory state is consistent with the inhibition of the long-latency P.C.A. reaction by induction of antibodies reacting with -the human reaginic antibodies.
addicted to filon. At present he needs to take 20-25 tablets and knows that daily. He has been taking them for two years if he suddenly stops he gets " the shakes " as the major component of an unpleasant withdrawal syndrome. As we have not yet received his old notes it is impossible to check everything he tells us. The estimated daily consumption of 20-25 tablets may well be the true figure, however, for after an appearance in court concerned with obtaining his drug from four other doctors, we are pretty sure that at the moment we are his only source of supply. SEÒNAID SEONAID I. 1. D. BIRD NEVIL H. SILVERTON. Leeds 8.
INHIBITION OF REAGIN-INDUCED PASSIVE CUTANEOUS ANAPHYLAXIS SIR,-The results of Dr. Radermecker and Dr. Goodfriend (Nov. 16, p. 1086) confirm our previous report of the development of a refractory state in monkeys to repeated long-latency
passive
cutaneous
anaphylaxis (P.C.A.).l They object
to our
tentative explanation that this is the result of development of rhesus antibodies against human reagin which inhibit cell fixation. Their conclusion is apparently based on their data demonstrating that such inhibition follows the administration of either normal human or rabbit sera to monkeys. They agree that an immunological mechanism is the most likely explanation for the phenomenon in view of the latent period and minimal volumes of heterologous sera required for induction of refractoriness in their experiments. The objection to our proposed explanation appears to be based on the assumption that the normal rabbit and normal human sera do not contain reagin and therefore cannot result in production of an inhibiting
monkey anti-reagin antibody. Several factors must be considered. Antibodies with reaginic activity occur in many species including man, sub-human primates, dogs, and 3 species of rodents. The rhesus and canine reaginic antibodies appear to reside in an immunoglobulin class analogous to yE.3 It appears likely that reaginic antibody is present in many, perhaps all, mammalian species. The absence of reaginic antibody in the normal human and rabbit sera used in the experiments of Dr. Radermecker and Dr. Goodfriend was not established. It is entirely possible that reaginic antibody in the rabbit serum immunised the monkeys against determinants on rabbit reagin that are either identical or very similar to those on human reagin. These antibodies could inhibit the fixation of human reagin to cells in monkey skin. Cross-reactivity of this type is well established. For example, rabbit antisera against human immunoglobulins have been used to identify canine yA and yM.4 Finally, it is not necessary for the normal rabbit and human
sera to
contain
reagin if cross-reacting antibodies are a satisfactory explanation for the inhibition of long-latency P.C.A. Monkeys injected with rabbit and human sera may make antibodies against common light-chain determinants present on the human or rabbit G, A, or M immunoglobulins. These monkey anti-light-chain antibodies would react with light-chain determinants on human reaginic antibodies, either inhibiting cell fixation in an as yet undefined manner or leading to phagocytosis of the reaginantibody complex. The failure of egg albumin to result in the Patterson, R., Fink, J. N., Nishimura, E. T., Pruzansky, J. J. J. clin. Invest. 1965, 44, 140. 2. Patterson, R. in Laboratory Models of Reagin Allergy in Progress in Allergy, vol. XIII (edited by P. Kallos and B. H. Waksman). Basle (in the press). 3. Patterson, R., Roberts, R., Pruzansky, J. J. J. Immun. (in the press). 4. Vaerman, J. P., Heremans, J. F. Immunochemistry, 1968, 5, 425. 1.
Emest S. Bazley Allergy Research Laboratories, Department of Medicine, Northwestern University, Chicago, Illinois 60611.
ROY PATTERSON J. J. PRUZANSKY.
METHOTREXATE IN PSORIASIS
SIR,-Dr. Nyfors (Dec. 7, p. 1251) is certainly right in his belief that more deaths have occurred as a result of the use of methotrexate in psoriasis than havebeen reported. In our papery to which he referred, we stressed the high rate of morbidity induced by both methotrexate and systemic steroids in patients with generalised pustular psoriasis, and the strong tendency of this syndrome to spontaneous remission. We also produced evidence which suggests that the early systemic use of steroids reduces the chance of such a remission and, although possibly controlling the disease in the short term, makes the long-term management more difficult. We believe that methotrexate is particularly valuable in allowing such steroid-dependent patients to be weaned off their steroid. During this procedure the two drugs have to be given together for a few weeks, but we would never give the two together for longer periods in increasing doses. The unwanted effects are additive, and, at the levels of dosage described by Dr. Nyfors, severe toxicity is almost inevitable, especially in an ill patient who may be dehydrated, hypoproteinaemic, or on other drugs such as salicylatesand who may have developed impaired renal function. In such a situation the iatrogenic risk to the patient may become greater than the risk from the untreated disease. In view of these facts we advocate a conservative and expectant approach to the management of generalised pustular psoriasis, unless high fever, severe toxicity, and nursing difficulties combine to immediately threaten life or render it intolerable. In the less acute cases-the majority-of generalised pustular psoriasis, skilled nursing care in hospital and the use of only bland local applications without steroids or methotrexate for 2 or even 3 months may be in the patient’s best interests in the hope that spontaneous remission will occur. This particularly applies if long-standing banal psoriasis preceded the pustular phase. In the report of another death in these columns recently,3 the author’s own description makes it impossible to escape the conclusion that death was due to simple overdosage. Methotrexate is an invaluable drug in the management of the very small minority of psoriatics with life-threatening or chronically disabling forms of the disease, but the utmost care must be exercised in its use. HARVEY BAKER Institute of Dermatology, TERENCE J. RYAN. Lisle Street, London W.C.2.
PREVENTING AIR-EMBOLISM AFTER ABDOMINAL INJURY SIR,-The continued high mortality associated with blunt liver trauma has been attributed to air-embolism.4 This report, and the findings in our own patients with hepatic trauma, have stimulated us to study this problem in dogs. Our previous experience with a double - ballooned inferior - vena - cava catheter ’ 6 suggested its possibilities in preventing both 1. Ryan, T. J., Baker, H. Br. J. Derm. in the press. 2. Baker, H. Lancet, 1968, i, 205. 3. Sanderson, M. ibid, p. 1251. 4. Aronsèn, K. F., Bengmark, S., Dahlgren, S., Engevik, L., Ericsson, Thoren, L. Surgery, St. Louis, 1968, 63, 236. 5. Rousselot, L. M., Grossi, C. E., Slattery, J., Rossi, P., Conte, A. Ruzicka, F. F., Jr. Surgery Gynec. Obstet. 1964, 118, 1295. 6. Rousselot, L. M., Grossi, C. E., Slattery, J., Rossi, P., Ruzicka, F. Jr., Prytz, B. J. Am. med. Ass. 1965, 191, 707.
B., J., F.,
1396 and air-embolism by proper placement and inflation. We have observed in dogs that, when the central venous pressure (c.v.P.) falls into the range of 0-1 cm. of saline, air-embolism consistently results from lacerations of the hepatic veins or infrahepatic vena cava. On raising the c.v.p. to 4-5 cm. of saline the aspiration of air promptly stopped, and it never occurred above this level. The double-ballooned catheter uniformly controlled air-embolism and assisted in controlling haemorrhage. From a clinical standpoint this experience emphasises the importance of re-establishing a normal c.v.p. whenever possible before exploring the abdomen of any patient felt to have a laceration of the liver or great vessels. DAVID BEFELER WILLIAM F. MITTY, Jr. St. Vincent’s Hospital CARLO GROSSI and Medical Center of New York, THOMAS NEALON. New York 10011.
hxmorrhage
ALKALINE PHOSPHATASE IN LIVER CIRRHOSIS AND RECTAL CANCER SIR Two recent reports 12 on the increased level of intestinal alkaline phosphatase in serum of patients with certain types of steatorrhoea prompt me to suggest that this rise might be due to reduced catabolism. Additional amounts of this isoenzyme seem to be swept into the circulation via the thoracic duct during intestinal resorption of fat,3-6 especially long-chain triglycerides .6s In normal persons the resultant increased serum-level of alkaline phosphatase becomes normal again after six to ten hours.4 ’7 In patients with liver cirrhosis the catabolism of this isoenzyme seems to be reduced; therefore the fat-induced increase is prolonged and becomes normal after three to six days.’ My colleagues and I have electrophoretically assayed raised activity of intestinal alkaline phosphatase in fasting blood in order to diagnose liver cirrhosis.8 The levels of intestinal alkaline phosphatase reached in serum after a fatty mean are genetically controlled and linked to the ABH system the ABO blood-groups and in normals 45 and patients with liver cirrhosis,8 as are the intestinal concentrations of alkaline phosphatase.9 The participation of the metabolically very active small intestine in enzyme catabolism is known.1o In contrast to other enzymes, I could not find reports on alkalinephosphatase catabolism in the intestine either in normal persons or, for instance, in patients with malabsorption-in this condition,12and in intestinal lymphoma," 12 genetic factors and possibly impaired catabolism seem sometimes to be responsible for raised serum-levels of intestinal alkaline
phosphatase. patient with liver cirrhosis I found an initially unrecognised alkaline-phosphatase fraction with an electrophoretic mobility intermediate between that of the normal liver and intestinal fractions, as reported by Professor Dent and colleagues in their case, after storage for three months at — 20°C. Was this a degradation artefact ? By routinely analysing sera of patients with raised alkalinephosphatase levels, I found a hitherto undescribed abnormal isoenzyme by electrophoretic separation in two patients with metastasising gastric and rectal adenocarcinoma. In homogenates of five metastasising rectal carcinomas electrophoretically studied in consequence for abnormal phosIn the
1. 2. 3. 4.
5. 6. 7. 8. 9.
10. 11. 12.
serum
of
a
Yong, J. M. Lancet, 1966, i, 1132. Dent, C. E., Norris, T. St. M., Smith, R., Sutton, R. A. L., Temperley, J. M. ibid. 1968, i, 1333. Keiding, N. P. Clin. Sci. 1964, 26, 291. Langman, M. J. S., Leuthold, E., Robson, C. B., Harris, J., Luffman, J. E., Harris, H. Nature, Lond. 1967, 124, 699. Inglis, N. J., Krant, M. J., Fishman, W. H. Proc. Soc. exp. Biol. Med. 1967, 124, 699. Klein, U. E., Drube, H. Chr., Hansen, H. Th. Klin. Wschr. 1967, 45, 95. Klein, U. E. Unpublished. Klein, U. E., Drube, H. Chr., Hansen, H. Th. Verh. dt. Ges. inn. Med. 1967, 73, 241. Langman, M. J. S., Constantinopoulos, A., Bouchier, I. A. D. Nature, Lond. 1968, 217, 863. Fleisher, G. A., Wakim, K. G. Enzymol. biol. Clin. 1968, 9, 81. Ramot, B., Streifler, C. Lancet, 1966, ii, 587. Krikler, D. M. ibid. July 6, 1968, p. 51.
1, 3, 5: homogenates of 3 adenocarcinomas of rectum (1/2 w/v in distilled water, butanol extracted). 2, 4, 6: serum of patient with liver cirrhosis, for comparison.
phatases, similar abnormally fast migrating fractions were detected, not found in normal mucosa. Such abnormal phosphatase lines in serum seem to be rare, since in nineteen other patients, with widely metastasising gastrointestinal carcinomas, abnormal phosphatases arising from tumour tissue were not found. It is assumed that only in rare instances tumour phosphatase enters the serum in high concentration to become detectable by electrophoretic techniques. A basic parallel seems to be the placenta: placental alkaline phosphatase is found in the serum at the end of pregnancy, 114 when there is a large and regressing organ, with
high phosphatase content. A specific cancer phosphatase also found by Fishman et al.,15 and Timperley.16 First Department of Internal Medicine University of Kiel, West Germany.
was
U. E. KLEIN.
ACTIVITY IN CHOLESTATIC LIVER SiR,—Acocella et al. reported that bilirubin glucuronide can be converted to unconjugated bilirubin in vivo. Okolicsanyi et a1.18 reported analogous results, stressing an intrahepatic deconjugation of bilirubin glucuronide and the probable importance of hepatic &bgr;-glucuronidase. Raia, moreover, has demonstrated by histochemical methods an association of &bgr;-glucuronidase with the bilirubin granules in the liver.19 In agreement with these findings are our conclusions as to &bgr;-glucuronidase activity determined according to Fishmann 20 in hepatic tissue of Sprague Dawley rats at 12 days after ligature of the common bileduct. Hepatic -glucuronidase activity was increased in rats whose bileducts had been ligated. The mean concentration of (-glucuronidase activity was 166882029 µg. phenolphthalein liberated per g. per hour in 10 normal rats and 24529-2112 µg. phenolphthalein liberated
&bgr;-GLUCURONIDASE
per g. per hour in 10 icteric rats (p < 0-01). These results are in good agreement with the increase of 13. 14. 15.
16. 17. 18. 19. 20.
Klein, U. E. Clin. Chim. Acta, 1967, 16, 163. Beckman, L., Bjorling, G., Christodoulou, C. Acta genet. Statist. Med. 1966, 26, 59. Fishman, W. H., Inglis, N. I., Stolbach, L. L., Krant, M. J. Cancer Res. 1968, 28, 150. Fishman, W. H., Inglis, N. I., Green, S., Anstiss, C. L., Gosh, N. K., Reif, A. E., Rustigan, R., Krant, M. J., Stolbach, L. L. Nature, Lond. 1968, 219, 697. Timperley, W. R. Lancet, August 10, 1968, p. 356. Acocella, G., Tenconi, L. T., Armas-Merino, R., Raia, S., Billing, B. ibid. 1968, i, 68. Okolicsanyi, L., Magnenat, P., Frei, J. ibid. p. 1173. Raia, S. in Acocella G., Tenconi, L. T., Armas-Merino, R., Raia, S., Billing, B. ibid. p. 68. Fishman, W. H. in Methods of Enzymatic Analysis (edited by H. W. Bergmeyer), Weinheim, 1963.
SIR,-We think it important to describe an unpublicised side-effect of the drug mixture ’Filon ’ (phenmetrazine theoclate 30 mg., phenbutrazate hydrochloride 20 mg.), said to have the same anorectic action as ’Preludin’ (phenmetrazine hydrochloride 25 mg.) but not its addictive properties. We have a new patient, a man of 33, who is without doubt
induction of the refractory state is consistent with the inhibition of the long-latency P.C.A. reaction by induction of antibodies reacting with -the human reaginic antibodies.
addicted to filon. At present he needs to take 20-25 tablets and knows that daily. He has been taking them for two years if he suddenly stops he gets " the shakes " as the major component of an unpleasant withdrawal syndrome. As we have not yet received his old notes it is impossible to check everything he tells us. The estimated daily consumption of 20-25 tablets may well be the true figure, however, for after an appearance in court concerned with obtaining his drug from four other doctors, we are pretty sure that at the moment we are his only source of supply. SEÒNAID SEONAID I. 1. D. BIRD NEVIL H. SILVERTON. Leeds 8.
INHIBITION OF REAGIN-INDUCED PASSIVE CUTANEOUS ANAPHYLAXIS SIR,-The results of Dr. Radermecker and Dr. Goodfriend (Nov. 16, p. 1086) confirm our previous report of the development of a refractory state in monkeys to repeated long-latency
passive
cutaneous
anaphylaxis (P.C.A.).l They object
to our
tentative explanation that this is the result of development of rhesus antibodies against human reagin which inhibit cell fixation. Their conclusion is apparently based on their data demonstrating that such inhibition follows the administration of either normal human or rabbit sera to monkeys. They agree that an immunological mechanism is the most likely explanation for the phenomenon in view of the latent period and minimal volumes of heterologous sera required for induction of refractoriness in their experiments. The objection to our proposed explanation appears to be based on the assumption that the normal rabbit and normal human sera do not contain reagin and therefore cannot result in production of an inhibiting
monkey anti-reagin antibody. Several factors must be considered. Antibodies with reaginic activity occur in many species including man, sub-human primates, dogs, and 3 species of rodents. The rhesus and canine reaginic antibodies appear to reside in an immunoglobulin class analogous to yE.3 It appears likely that reaginic antibody is present in many, perhaps all, mammalian species. The absence of reaginic antibody in the normal human and rabbit sera used in the experiments of Dr. Radermecker and Dr. Goodfriend was not established. It is entirely possible that reaginic antibody in the rabbit serum immunised the monkeys against determinants on rabbit reagin that are either identical or very similar to those on human reagin. These antibodies could inhibit the fixation of human reagin to cells in monkey skin. Cross-reactivity of this type is well established. For example, rabbit antisera against human immunoglobulins have been used to identify canine yA and yM.4 Finally, it is not necessary for the normal rabbit and human
sera to
contain
reagin if cross-reacting antibodies are a satisfactory explanation for the inhibition of long-latency P.C.A. Monkeys injected with rabbit and human sera may make antibodies against common light-chain determinants present on the human or rabbit G, A, or M immunoglobulins. These monkey anti-light-chain antibodies would react with light-chain determinants on human reaginic antibodies, either inhibiting cell fixation in an as yet undefined manner or leading to phagocytosis of the reaginantibody complex. The failure of egg albumin to result in the Patterson, R., Fink, J. N., Nishimura, E. T., Pruzansky, J. J. J. clin. Invest. 1965, 44, 140. 2. Patterson, R. in Laboratory Models of Reagin Allergy in Progress in Allergy, vol. XIII (edited by P. Kallos and B. H. Waksman). Basle (in the press). 3. Patterson, R., Roberts, R., Pruzansky, J. J. J. Immun. (in the press). 4. Vaerman, J. P., Heremans, J. F. Immunochemistry, 1968, 5, 425. 1.
Emest S. Bazley Allergy Research Laboratories, Department of Medicine, Northwestern University, Chicago, Illinois 60611.
ROY PATTERSON J. J. PRUZANSKY.
METHOTREXATE IN PSORIASIS
SIR,-Dr. Nyfors (Dec. 7, p. 1251) is certainly right in his belief that more deaths have occurred as a result of the use of methotrexate in psoriasis than havebeen reported. In our papery to which he referred, we stressed the high rate of morbidity induced by both methotrexate and systemic steroids in patients with generalised pustular psoriasis, and the strong tendency of this syndrome to spontaneous remission. We also produced evidence which suggests that the early systemic use of steroids reduces the chance of such a remission and, although possibly controlling the disease in the short term, makes the long-term management more difficult. We believe that methotrexate is particularly valuable in allowing such steroid-dependent patients to be weaned off their steroid. During this procedure the two drugs have to be given together for a few weeks, but we would never give the two together for longer periods in increasing doses. The unwanted effects are additive, and, at the levels of dosage described by Dr. Nyfors, severe toxicity is almost inevitable, especially in an ill patient who may be dehydrated, hypoproteinaemic, or on other drugs such as salicylatesand who may have developed impaired renal function. In such a situation the iatrogenic risk to the patient may become greater than the risk from the untreated disease. In view of these facts we advocate a conservative and expectant approach to the management of generalised pustular psoriasis, unless high fever, severe toxicity, and nursing difficulties combine to immediately threaten life or render it intolerable. In the less acute cases-the majority-of generalised pustular psoriasis, skilled nursing care in hospital and the use of only bland local applications without steroids or methotrexate for 2 or even 3 months may be in the patient’s best interests in the hope that spontaneous remission will occur. This particularly applies if long-standing banal psoriasis preceded the pustular phase. In the report of another death in these columns recently,3 the author’s own description makes it impossible to escape the conclusion that death was due to simple overdosage. Methotrexate is an invaluable drug in the management of the very small minority of psoriatics with life-threatening or chronically disabling forms of the disease, but the utmost care must be exercised in its use. HARVEY BAKER Institute of Dermatology, TERENCE J. RYAN. Lisle Street, London W.C.2.
PREVENTING AIR-EMBOLISM AFTER ABDOMINAL INJURY SIR,-The continued high mortality associated with blunt liver trauma has been attributed to air-embolism.4 This report, and the findings in our own patients with hepatic trauma, have stimulated us to study this problem in dogs. Our previous experience with a double - ballooned inferior - vena - cava catheter ’ 6 suggested its possibilities in preventing both 1. Ryan, T. J., Baker, H. Br. J. Derm. in the press. 2. Baker, H. Lancet, 1968, i, 205. 3. Sanderson, M. ibid, p. 1251. 4. Aronsèn, K. F., Bengmark, S., Dahlgren, S., Engevik, L., Ericsson, Thoren, L. Surgery, St. Louis, 1968, 63, 236. 5. Rousselot, L. M., Grossi, C. E., Slattery, J., Rossi, P., Conte, A. Ruzicka, F. F., Jr. Surgery Gynec. Obstet. 1964, 118, 1295. 6. Rousselot, L. M., Grossi, C. E., Slattery, J., Rossi, P., Ruzicka, F. Jr., Prytz, B. J. Am. med. Ass. 1965, 191, 707.
B., J., F.,
1396 and air-embolism by proper placement and inflation. We have observed in dogs that, when the central venous pressure (c.v.P.) falls into the range of 0-1 cm. of saline, air-embolism consistently results from lacerations of the hepatic veins or infrahepatic vena cava. On raising the c.v.p. to 4-5 cm. of saline the aspiration of air promptly stopped, and it never occurred above this level. The double-ballooned catheter uniformly controlled air-embolism and assisted in controlling haemorrhage. From a clinical standpoint this experience emphasises the importance of re-establishing a normal c.v.p. whenever possible before exploring the abdomen of any patient felt to have a laceration of the liver or great vessels. DAVID BEFELER WILLIAM F. MITTY, Jr. St. Vincent’s Hospital CARLO GROSSI and Medical Center of New York, THOMAS NEALON. New York 10011.
hxmorrhage
ALKALINE PHOSPHATASE IN LIVER CIRRHOSIS AND RECTAL CANCER SIR Two recent reports 12 on the increased level of intestinal alkaline phosphatase in serum of patients with certain types of steatorrhoea prompt me to suggest that this rise might be due to reduced catabolism. Additional amounts of this isoenzyme seem to be swept into the circulation via the thoracic duct during intestinal resorption of fat,3-6 especially long-chain triglycerides .6s In normal persons the resultant increased serum-level of alkaline phosphatase becomes normal again after six to ten hours.4 ’7 In patients with liver cirrhosis the catabolism of this isoenzyme seems to be reduced; therefore the fat-induced increase is prolonged and becomes normal after three to six days.’ My colleagues and I have electrophoretically assayed raised activity of intestinal alkaline phosphatase in fasting blood in order to diagnose liver cirrhosis.8 The levels of intestinal alkaline phosphatase reached in serum after a fatty mean are genetically controlled and linked to the ABH system the ABO blood-groups and in normals 45 and patients with liver cirrhosis,8 as are the intestinal concentrations of alkaline phosphatase.9 The participation of the metabolically very active small intestine in enzyme catabolism is known.1o In contrast to other enzymes, I could not find reports on alkalinephosphatase catabolism in the intestine either in normal persons or, for instance, in patients with malabsorption-in this condition,12and in intestinal lymphoma," 12 genetic factors and possibly impaired catabolism seem sometimes to be responsible for raised serum-levels of intestinal alkaline
phosphatase. patient with liver cirrhosis I found an initially unrecognised alkaline-phosphatase fraction with an electrophoretic mobility intermediate between that of the normal liver and intestinal fractions, as reported by Professor Dent and colleagues in their case, after storage for three months at — 20°C. Was this a degradation artefact ? By routinely analysing sera of patients with raised alkalinephosphatase levels, I found a hitherto undescribed abnormal isoenzyme by electrophoretic separation in two patients with metastasising gastric and rectal adenocarcinoma. In homogenates of five metastasising rectal carcinomas electrophoretically studied in consequence for abnormal phosIn the
1. 2. 3. 4.
5. 6. 7. 8. 9.
10. 11. 12.
serum
of
a
Yong, J. M. Lancet, 1966, i, 1132. Dent, C. E., Norris, T. St. M., Smith, R., Sutton, R. A. L., Temperley, J. M. ibid. 1968, i, 1333. Keiding, N. P. Clin. Sci. 1964, 26, 291. Langman, M. J. S., Leuthold, E., Robson, C. B., Harris, J., Luffman, J. E., Harris, H. Nature, Lond. 1967, 124, 699. Inglis, N. J., Krant, M. J., Fishman, W. H. Proc. Soc. exp. Biol. Med. 1967, 124, 699. Klein, U. E., Drube, H. Chr., Hansen, H. Th. Klin. Wschr. 1967, 45, 95. Klein, U. E. Unpublished. Klein, U. E., Drube, H. Chr., Hansen, H. Th. Verh. dt. Ges. inn. Med. 1967, 73, 241. Langman, M. J. S., Constantinopoulos, A., Bouchier, I. A. D. Nature, Lond. 1968, 217, 863. Fleisher, G. A., Wakim, K. G. Enzymol. biol. Clin. 1968, 9, 81. Ramot, B., Streifler, C. Lancet, 1966, ii, 587. Krikler, D. M. ibid. July 6, 1968, p. 51.
1, 3, 5: homogenates of 3 adenocarcinomas of rectum (1/2 w/v in distilled water, butanol extracted). 2, 4, 6: serum of patient with liver cirrhosis, for comparison.
phatases, similar abnormally fast migrating fractions were detected, not found in normal mucosa. Such abnormal phosphatase lines in serum seem to be rare, since in nineteen other patients, with widely metastasising gastrointestinal carcinomas, abnormal phosphatases arising from tumour tissue were not found. It is assumed that only in rare instances tumour phosphatase enters the serum in high concentration to become detectable by electrophoretic techniques. A basic parallel seems to be the placenta: placental alkaline phosphatase is found in the serum at the end of pregnancy, 114 when there is a large and regressing organ, with
high phosphatase content. A specific cancer phosphatase also found by Fishman et al.,15 and Timperley.16 First Department of Internal Medicine University of Kiel, West Germany.
was
U. E. KLEIN.
ACTIVITY IN CHOLESTATIC LIVER SiR,—Acocella et al. reported that bilirubin glucuronide can be converted to unconjugated bilirubin in vivo. Okolicsanyi et a1.18 reported analogous results, stressing an intrahepatic deconjugation of bilirubin glucuronide and the probable importance of hepatic &bgr;-glucuronidase. Raia, moreover, has demonstrated by histochemical methods an association of &bgr;-glucuronidase with the bilirubin granules in the liver.19 In agreement with these findings are our conclusions as to &bgr;-glucuronidase activity determined according to Fishmann 20 in hepatic tissue of Sprague Dawley rats at 12 days after ligature of the common bileduct. Hepatic -glucuronidase activity was increased in rats whose bileducts had been ligated. The mean concentration of (-glucuronidase activity was 166882029 µg. phenolphthalein liberated per g. per hour in 10 normal rats and 24529-2112 µg. phenolphthalein liberated
&bgr;-GLUCURONIDASE
per g. per hour in 10 icteric rats (p < 0-01). These results are in good agreement with the increase of 13. 14. 15.
16. 17. 18. 19. 20.
Klein, U. E. Clin. Chim. Acta, 1967, 16, 163. Beckman, L., Bjorling, G., Christodoulou, C. Acta genet. Statist. Med. 1966, 26, 59. Fishman, W. H., Inglis, N. I., Stolbach, L. L., Krant, M. J. Cancer Res. 1968, 28, 150. Fishman, W. H., Inglis, N. I., Green, S., Anstiss, C. L., Gosh, N. K., Reif, A. E., Rustigan, R., Krant, M. J., Stolbach, L. L. Nature, Lond. 1968, 219, 697. Timperley, W. R. Lancet, August 10, 1968, p. 356. Acocella, G., Tenconi, L. T., Armas-Merino, R., Raia, S., Billing, B. ibid. 1968, i, 68. Okolicsanyi, L., Magnenat, P., Frei, J. ibid. p. 1173. Raia, S. in Acocella G., Tenconi, L. T., Armas-Merino, R., Raia, S., Billing, B. ibid. p. 68. Fishman, W. H. in Methods of Enzymatic Analysis (edited by H. W. Bergmeyer), Weinheim, 1963.