259 these concentrations of the resins. Thus, on a weight basis, colestipol was some four times more effective. Both cholestyramine and colestipol hydrochloride are basic, high molecular weight, and insoluble anionic exchange resins. They have a strong affinity for acids and may absorb neutral substances, but they have little affinity for basic substances. Our results indicate that these anion-exchange resins bind the toxin which is now implicated in antibiotic-associated colitis, thus providing a presumptive explanation for the favourable effects previously observed with cholestyramine treatment. We have also tested the effect of anion-exchange resins on enterotoxins of Escherichia coli, Vibrio cholerce, Shigella dysenterice, and Staphylococcus aureus (type B toxin). No binding was observed, suggesting that the toxin of C. difficile is acidic or neutral while other toxins are either neutral or basic. This zoo,
study was supported by a grant Michigan.
from the
Tufts University School of Medicine, and Boston Veterans Administration Hospital, Boston, Massachusetts, U.S.A.
Upjohn Co.,
Kalama-
TE WEN CHANG ANDREW B. ONDERDONK JOHN G. BARTLETT
We are left with the conclusion that leuksmic infiltration of the testis of a microscopic type may well serve as a sanctuary from which cells reseed the marrow or central nervous system. These cells may well remain in prolonged resting phase in an environment which has been significantly altered by tissue damage. Of the series of biopsies to date there has only been one occasion where a biopsy which was considered to be equivocal was followed, approximately 8 months later by haematological relapse and, on review of all sections of that initial testicular biopsy sample, one small focus of lymphoid cells was found. Over a period of a year no other patient with a negative biopsy has yet shown hsmatological or meningeal relapse. Longer follow-up will show whether the 15% of patients with clinically normal testis but positive biopsies will be salvaged by intensive local treatment and prolonged systemic therapy. The poor prognosis for patients with overt testicular infiltration is a strong argument in favour of prophylaxis. Department of Child Life and Health,
University of Edinburgh Edinburgh EH9 1UW
O. B. EDEN
HEPATIC BRUITS IN LIVER TUMOURS TESTICULAR INFILTRATES IN CHILDHOOD LEUKÆMIA
SIR,- Your editorial and the paper by Dr Baumer and Dr Mott in the issue of July 15 raise some important points which require further clarification. Following our initial reportl to the M.R.C. Working Party on Childhood Leukaemia we have further analysed the 29 patients who presented with isolated infiltration. Their actuarial disease-free survival at 2 years is only 20%. 7 patients are alive, free of disease, at follow-ups of 13-43 months. 7 more are alive having had at least one relapse. Your editorial implied that overt testicular infiltration suggests systemic disease. Our evidence is not conclusive. Some of the 29 relapsed very early, suggesting that the disease was indeed widespread at the time that the testis was noted to be swollen. Others received further chemotherapy, which may have suppressed systemic disease, and relapsed when that therapy was discontinued. None of this, however, explains why boys fare worse than girls (there being at least 30% difference in 5-year disease-free survival). In our initial survey we found that the addition of cyclophosphamide to treatment regimens increased the risk of testicular infiltration. Morris-Jones et al.,2 in a small series, have reported histological findings consequent upon chemotherapy ; they found a relationship between cytarabine and cyclophosphamide and decreasing tubular fertility and increasing interstitial fibrosis. We have now reviewed nearly 200 routine testicular biopsies on boys just completing courses of chemotherapy and, although the analysis is preliminary, we are finding a similar increased damage effect of cyclophosphamide and possibility cytarabine.3 It is curious that a drug such as cyclophosphamide which definitely causes damage within the sensitive testis has also been implicated as leading to an increased incidence of leukaemic infiltration in that organ. Perhaps leukxmic cells initially seeded in the testis, as in other organs, survive preferentially when tissue damage occurs. The histological findings of Mathe, Sharp, Simone, and their colleagues (cited in your editorial) imply that leukaemic cells are found throughout the body even when patients are apparently in complete remission. This does not explain sex difference, though Morris-Jones et al. have demonstrated that chemotherapy does not apparently affect most boys in terms of hormonal function.
SIR,-Arterial murmurs can be heard over the abdomen in various diseases and sometimes even in normal patients with persons.’ 1 Clain et al.’ reported that in some liver diseases, such as hepatocellular carcinoma and alcoholic hepatitis, abdominal bruits were also auscultated over the liver and that they contributed to the differential diagnosis. There have been few reports on hepatic bruits in malignant liver tumours other than hepatocellular carcinoma. We have noted hepatic bruits in a case of intrahepatic cholangiocarcinoma and in a case of metastatic liver carcinoma. The murmurs were confirmed by sound recordings. A 38-year-old woman was admitted with anorexia and icterus. The liver was palpable 3.5fingerbreadths below the right costal margin. A continuous murmur with late-systolic accentuation was heard over the liver in the epigastrium. After a month the patient died. At necropsy there was an adenocarcinoma arising in the bileduct at the hepatic hilum, which infiltrated several centimetres into the liver, with multiple intrahepatic metastases of less than walnut size. A 34-year-old woman was operated on palliatively for an adenoid cystic carcinoma of the right submaxillary gland. After 3 months she was admitted with an abdominal tumour. The liver was palpable 8 fingerbreadths below the right costal margin. A late-systolic murmur was heard over the liver in the epigastrium. Laparoscopy and abdominal angiography confirmed a large liver tumour due to metastasis of the adenoid carcinoma. Tumours other than hepatocellular carcinoma should be considered when an arterial murmur is heard in the upper abdomen.
cystic
Second Department of Internal Medicine, Faculty of Medicine, Tokyo University, Tokyo 113, Japan
over the liver suggests hepatoma3-6 do not mention liver bruit as a feature series though large of this condition. This physical sign could prove especially
SIR,-A systolic bruit
even
Rivin, A. U.J. Am. med. Ass. 1972, 221, 688. Watson, W. C., Williams, P. B., Duffy, G. Ann. intern. Med. 1973, 79, 211. 3. Clain, D., Wartnaby, K., Sherlock, S. Lancet, 1966, ii, 516. 4. Mills, P. E., Jr, Calif. Med. 1967, 107, 270. 5. Shah, M. J., Agarwal, A. K., Manvi, K. N.J. Ass. Physns India, 1967, 15,
M., Peto, J. Br. med.
1. 2.
I. M., Marsden, H. B., Lendon, M., Shalet, S. M. Proc. Am. Soc. clin. Oncol. 1978, 19, 365. 3. Gowing, N. F. C., Eden, O. B., Initial Report of Testicular Tumor Panel to the M.R.C. Working Party on Childhood Leukæmia. April, 1978.
6.
1.
Eden, O, B., Hardisty, R. M, Innes, E. M., Kay, H.
2.
J. 1978, i, 334. Morris-Jones, P. H., Hann,
E.
TATSUYA MOTOKI TERUMI HAYASHI YOSHIHISA KATOH TSUGUYA SAKAMOTO TADANAO TAKEDA SATORU MURAO
483.
Tsega, E. E. Afr. med. J. 1977, 54, 281.
study was supported by a grant Michigan.
from the
Tufts University School of Medicine, and Boston Veterans Administration Hospital, Boston, Massachusetts, U.S.A.
Upjohn Co.,
Kalama-
TE WEN CHANG ANDREW B. ONDERDONK JOHN G. BARTLETT
We are left with the conclusion that leuksmic infiltration of the testis of a microscopic type may well serve as a sanctuary from which cells reseed the marrow or central nervous system. These cells may well remain in prolonged resting phase in an environment which has been significantly altered by tissue damage. Of the series of biopsies to date there has only been one occasion where a biopsy which was considered to be equivocal was followed, approximately 8 months later by haematological relapse and, on review of all sections of that initial testicular biopsy sample, one small focus of lymphoid cells was found. Over a period of a year no other patient with a negative biopsy has yet shown hsmatological or meningeal relapse. Longer follow-up will show whether the 15% of patients with clinically normal testis but positive biopsies will be salvaged by intensive local treatment and prolonged systemic therapy. The poor prognosis for patients with overt testicular infiltration is a strong argument in favour of prophylaxis. Department of Child Life and Health,
University of Edinburgh Edinburgh EH9 1UW
O. B. EDEN
HEPATIC BRUITS IN LIVER TUMOURS TESTICULAR INFILTRATES IN CHILDHOOD LEUKÆMIA
SIR,- Your editorial and the paper by Dr Baumer and Dr Mott in the issue of July 15 raise some important points which require further clarification. Following our initial reportl to the M.R.C. Working Party on Childhood Leukaemia we have further analysed the 29 patients who presented with isolated infiltration. Their actuarial disease-free survival at 2 years is only 20%. 7 patients are alive, free of disease, at follow-ups of 13-43 months. 7 more are alive having had at least one relapse. Your editorial implied that overt testicular infiltration suggests systemic disease. Our evidence is not conclusive. Some of the 29 relapsed very early, suggesting that the disease was indeed widespread at the time that the testis was noted to be swollen. Others received further chemotherapy, which may have suppressed systemic disease, and relapsed when that therapy was discontinued. None of this, however, explains why boys fare worse than girls (there being at least 30% difference in 5-year disease-free survival). In our initial survey we found that the addition of cyclophosphamide to treatment regimens increased the risk of testicular infiltration. Morris-Jones et al.,2 in a small series, have reported histological findings consequent upon chemotherapy ; they found a relationship between cytarabine and cyclophosphamide and decreasing tubular fertility and increasing interstitial fibrosis. We have now reviewed nearly 200 routine testicular biopsies on boys just completing courses of chemotherapy and, although the analysis is preliminary, we are finding a similar increased damage effect of cyclophosphamide and possibility cytarabine.3 It is curious that a drug such as cyclophosphamide which definitely causes damage within the sensitive testis has also been implicated as leading to an increased incidence of leukaemic infiltration in that organ. Perhaps leukxmic cells initially seeded in the testis, as in other organs, survive preferentially when tissue damage occurs. The histological findings of Mathe, Sharp, Simone, and their colleagues (cited in your editorial) imply that leukaemic cells are found throughout the body even when patients are apparently in complete remission. This does not explain sex difference, though Morris-Jones et al. have demonstrated that chemotherapy does not apparently affect most boys in terms of hormonal function.
SIR,-Arterial murmurs can be heard over the abdomen in various diseases and sometimes even in normal patients with persons.’ 1 Clain et al.’ reported that in some liver diseases, such as hepatocellular carcinoma and alcoholic hepatitis, abdominal bruits were also auscultated over the liver and that they contributed to the differential diagnosis. There have been few reports on hepatic bruits in malignant liver tumours other than hepatocellular carcinoma. We have noted hepatic bruits in a case of intrahepatic cholangiocarcinoma and in a case of metastatic liver carcinoma. The murmurs were confirmed by sound recordings. A 38-year-old woman was admitted with anorexia and icterus. The liver was palpable 3.5fingerbreadths below the right costal margin. A continuous murmur with late-systolic accentuation was heard over the liver in the epigastrium. After a month the patient died. At necropsy there was an adenocarcinoma arising in the bileduct at the hepatic hilum, which infiltrated several centimetres into the liver, with multiple intrahepatic metastases of less than walnut size. A 34-year-old woman was operated on palliatively for an adenoid cystic carcinoma of the right submaxillary gland. After 3 months she was admitted with an abdominal tumour. The liver was palpable 8 fingerbreadths below the right costal margin. A late-systolic murmur was heard over the liver in the epigastrium. Laparoscopy and abdominal angiography confirmed a large liver tumour due to metastasis of the adenoid carcinoma. Tumours other than hepatocellular carcinoma should be considered when an arterial murmur is heard in the upper abdomen.
cystic
Second Department of Internal Medicine, Faculty of Medicine, Tokyo University, Tokyo 113, Japan
over the liver suggests hepatoma3-6 do not mention liver bruit as a feature series though large of this condition. This physical sign could prove especially
SIR,-A systolic bruit
even
Rivin, A. U.J. Am. med. Ass. 1972, 221, 688. Watson, W. C., Williams, P. B., Duffy, G. Ann. intern. Med. 1973, 79, 211. 3. Clain, D., Wartnaby, K., Sherlock, S. Lancet, 1966, ii, 516. 4. Mills, P. E., Jr, Calif. Med. 1967, 107, 270. 5. Shah, M. J., Agarwal, A. K., Manvi, K. N.J. Ass. Physns India, 1967, 15,
M., Peto, J. Br. med.
1. 2.
I. M., Marsden, H. B., Lendon, M., Shalet, S. M. Proc. Am. Soc. clin. Oncol. 1978, 19, 365. 3. Gowing, N. F. C., Eden, O. B., Initial Report of Testicular Tumor Panel to the M.R.C. Working Party on Childhood Leukæmia. April, 1978.
6.
1.
Eden, O, B., Hardisty, R. M, Innes, E. M., Kay, H.
2.
J. 1978, i, 334. Morris-Jones, P. H., Hann,
E.
TATSUYA MOTOKI TERUMI HAYASHI YOSHIHISA KATOH TSUGUYA SAKAMOTO TADANAO TAKEDA SATORU MURAO
483.
Tsega, E. E. Afr. med. J. 1977, 54, 281.
