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LIVER TUMOURS AND STEROID HORMONES
878 Certain lipid-containing viruses, particularly arboviruse: and vaccinia, have been shown to produce a hyperlipidxmiz in chick embryos. Work by Grossberg and O’Leary1 indicated that several viruses, inoculated into embryonated hen’s eggs, produced a hyperlipid.Tmia, characterised by high total lipids, with a striking increase in triglycerides and a decrease in phospholipids. In these embryos there was histological evidence of hepatitis. These findings led Grossberg et al. to postulate that the viral-induced lipidasmia resulted from deranged hepatic lipid bio-
synthesis. Virological studies
132 of our renal-transplant recipients during the past 4 years have indicated that virus infections are present in 80% of patients .3,44 The vast majority of these infections have been with herpesviruses, on
particularly cytomegalovirus, which are lipid-containing agents. Virus infection may persist for many months after successful transplantation and may be relatively asymptomatic. It is entirely possible that some of the patients of Dr Casaretto and his colleagues were shedding virus at the time of the lipid analyses. It would be of value to know whether their patients were studied virologically. Because of the frequency of viral infections in renaltransplant recipients, and because of experiments indicating that viruses can produce a hyperlipidaemia with evidence of liver dysfunction, it would be worth pursuing the possibility that the hyperlipideemia observed in successfully transplanted renal allograft recipients may indeed be related
to
virus infections.
University of Minnesota Health Science Center, Minneapolis, Minnesota 55455, U.S.A.
H. H. BALFOUR, JR. R. L. SIMMONS W. A. KRIVIT J. S. NAJARIAN.
LIVER TUMOURS AND STEROID HORMONES
SIR You raised the problem5 whether one should possible development of hepatoma to the previously
add the
of anabolic steroids on the liver. The appearance of a hepatoma has been described in patients with Fanconi’s anxmia who had been treated for many months with anabolic-androgenic steroids. 6-8 Johnson et al.8 reported hepatoma in a patient with postnecrotic cirrhosis-a condition which may favour the occurrence of hepatic carcinoma. Furthermore, Guy and Auslanderreported a patient who, twenty-four years before the onset of liver carcinoma, had received androgen therapy for only four months. We have observed a young girl with hepatoma whose case is relevant to this discussion.
reported effects
At the age of 7 years this girl was seen with a likely diagnosis of Fanconi’s anaemia, on the service of Prof. Jean Bernard (St. Louis Hospital, Paris). She had pancytopenia, retarded growth and pigmentation, syndactyly of the 2nd and 3rd toes, and microcephaly. Later the diagnosis was confirmed by the discovery of unilateral renal atrophy, pubertal failure, and dwarfism and an abnormally high incidence of chromosomal breaks. Splenectomy was performed at 8 years of age. This intervention permitted a longer interval between transfusions, followed by their complete withdrawal. 1. 2. 3.
4. 5. 6. 7. 8.
Grossberg, S. E., O’Leary, W. M. Nature, 1965, 208, 954. Grossberg, S. E., Roch, L. A., Frernan, F. E. Progr. immunobiol. Standard. (in the press). Lopez, C., Simmons, R. L., Mauer, S. M., Najarian, J. S., Good, R. A. Am. J. Med. 1974, 56, 280. Simmons, R. L., Lopez, C., Balfour, H., Uranga, V. M., Mauer, S. M., Najarian, J. S. Unpublished. Lancet, 1973, ii, 1481. Bernstein, M. S., Hunter, R. L., Yachnin, S. New Engl. J. Med. 1971, 284, 1135. Guy, J. T., Auslander, M. D. Lancet, 1973, i, 148. Johnson, F. L., Feagler, J. R., Lerner, K. G., Materus, P. W., Siegel, M., Hartman, J. R. ibid. 1972, ii, 1273.
In 1974, when the patient
was
24 years of age, while the
cause
right hypochondrial pain was being sought a nodular hepatomegaly was found. Peritoneoscopy, scanning with technetium and selenomethionine, and the presence of ct-fetoprotein favoured the diagnosis of hepatoma. This diagnosis was confirmed at of
necropsy. The hepatoma had
developed on a macronodular cirrhosis, hxmochromatosis which was apparently posttransfusional. Au antigen was not found. Careful questionmg of the patient’s family and all the doctors who had treated her indicated that she had never been given any androgen therapy. accompanied by
a
This observation means that a hepatoma may arise during the course of Fanconi’s anaemia, in the absence of androgen therapy. As in Johnson’s case 3, the hepatoma we report developed on a cirrhosis (probably post-necrotic). The high incidence of leukæmia 9,10 and solid turnouts 11 in patients with Fanconi’s anxmia, and in their families,
is well known. The finding of hepatoma may be a new indication of the " malignant potential " of this disease,12 possibly related to chromosome anomalies.13 Créteil University Medical
School, Department of Internal Medicine and Gastroenterology, Nouvel Hôpital, 94-Villeneuve St. Georges, France.
D. CATTAN P. VESIN J. WAUTIER R. KALIFAT S. MEIGNAN.
CLINDAMYCIN AND PSEUDOMEMBRANOUS COLITIS
SIR The report by Dr Scott and his colleagues
11
and
15-18
have drawn attention to the subsequent correspondence association of severe pseudomembranous colitis with treatment with clindamycin. We have recently seen a patient in whom the presentation was somewhat atypical. A 61-year-old woman started clindamycin 150 mg. 6-hourly and cloxacillin 500 mg. 6-hourly on March 7, 1974, for a superficial skin infection. On March 12 a total hip replacement was performed, and the immediate postoperative course was uneventful. On March 23 the patient complained of sudden onset of diarrhoea, nausea, vomiting, right-sided abdominal pain, and pyrexia, which soon settled with conservative treatment. The antibiotics were discontinued. The diarrhoea (about 3 loose stools a day) was adequately controlled with a kaolin preparation until April 8 when the patient became shocked with gross abdominal distension. Laparotomy and total colectomy with ileostomy was
performed. The bowel showed the characteristic naked-eye mucosal pseudomembranous colitis affecting the whole of the dilated colon and rectal stump, the terminal ileum being spared. Histological examination of the membranous plaque appearance of
confirmed the macroscopic diagnosis, and there was partial and full-thickness mucosal necrosis and patchy necrosis of the muscularis propria with intermuscular haemorrhage. There was thrombosis of the submucosal vessels and paracolic veins.
The case is unusual in that, although the diarrhoea started while the patient was receiving clindamycin, the symptoms were not severe and were readily controlled. It was not until 16 days after cessation of antibiotic therapy that the severe acute symptoms appeared. Perhaps in cases with a similar presentation not only should the present 9. Garriga, J., Crosby, N. H. Blood, 1959, 14, 1008. 10. Dosik, H., Hsu, L. Y., Todaroi, G. J., Lee, S. L., Kirschorn, K., Selirio, E. S. ibid. 1970, 36, 341. 11. Swift, M. R. Nature, 1971, 230, 370. 12. Fanconi G. Personal communication. 13. Schroeder, T. M., Anschutz, F., Knopp, A. Humangenetik, 1964 1, 194. 14. Scott, A. J., Nicholson, G. I., Kerr, A. R. Lancet, 1973, ii, 1232. 15. Sissons, J. G. P., Boulton-Jones, J. M., Peters, D. K. ibid. Feb. 2, 1974, p. 172. 16. Stroehlein, J. R., Hoffman, H. N., Sedlack, R. E., Newcomber A. D. ibid. Feb. 9, 1974, p. 221. 17. Temperley, J. M. ibid. 18. Sneddon, J. ibid.
synthesis. Virological studies
132 of our renal-transplant recipients during the past 4 years have indicated that virus infections are present in 80% of patients .3,44 The vast majority of these infections have been with herpesviruses, on
particularly cytomegalovirus, which are lipid-containing agents. Virus infection may persist for many months after successful transplantation and may be relatively asymptomatic. It is entirely possible that some of the patients of Dr Casaretto and his colleagues were shedding virus at the time of the lipid analyses. It would be of value to know whether their patients were studied virologically. Because of the frequency of viral infections in renaltransplant recipients, and because of experiments indicating that viruses can produce a hyperlipidaemia with evidence of liver dysfunction, it would be worth pursuing the possibility that the hyperlipideemia observed in successfully transplanted renal allograft recipients may indeed be related
to
virus infections.
University of Minnesota Health Science Center, Minneapolis, Minnesota 55455, U.S.A.
H. H. BALFOUR, JR. R. L. SIMMONS W. A. KRIVIT J. S. NAJARIAN.
LIVER TUMOURS AND STEROID HORMONES
SIR You raised the problem5 whether one should possible development of hepatoma to the previously
add the
of anabolic steroids on the liver. The appearance of a hepatoma has been described in patients with Fanconi’s anxmia who had been treated for many months with anabolic-androgenic steroids. 6-8 Johnson et al.8 reported hepatoma in a patient with postnecrotic cirrhosis-a condition which may favour the occurrence of hepatic carcinoma. Furthermore, Guy and Auslanderreported a patient who, twenty-four years before the onset of liver carcinoma, had received androgen therapy for only four months. We have observed a young girl with hepatoma whose case is relevant to this discussion.
reported effects
At the age of 7 years this girl was seen with a likely diagnosis of Fanconi’s anaemia, on the service of Prof. Jean Bernard (St. Louis Hospital, Paris). She had pancytopenia, retarded growth and pigmentation, syndactyly of the 2nd and 3rd toes, and microcephaly. Later the diagnosis was confirmed by the discovery of unilateral renal atrophy, pubertal failure, and dwarfism and an abnormally high incidence of chromosomal breaks. Splenectomy was performed at 8 years of age. This intervention permitted a longer interval between transfusions, followed by their complete withdrawal. 1. 2. 3.
4. 5. 6. 7. 8.
Grossberg, S. E., O’Leary, W. M. Nature, 1965, 208, 954. Grossberg, S. E., Roch, L. A., Frernan, F. E. Progr. immunobiol. Standard. (in the press). Lopez, C., Simmons, R. L., Mauer, S. M., Najarian, J. S., Good, R. A. Am. J. Med. 1974, 56, 280. Simmons, R. L., Lopez, C., Balfour, H., Uranga, V. M., Mauer, S. M., Najarian, J. S. Unpublished. Lancet, 1973, ii, 1481. Bernstein, M. S., Hunter, R. L., Yachnin, S. New Engl. J. Med. 1971, 284, 1135. Guy, J. T., Auslander, M. D. Lancet, 1973, i, 148. Johnson, F. L., Feagler, J. R., Lerner, K. G., Materus, P. W., Siegel, M., Hartman, J. R. ibid. 1972, ii, 1273.
In 1974, when the patient
was
24 years of age, while the
cause
right hypochondrial pain was being sought a nodular hepatomegaly was found. Peritoneoscopy, scanning with technetium and selenomethionine, and the presence of ct-fetoprotein favoured the diagnosis of hepatoma. This diagnosis was confirmed at of
necropsy. The hepatoma had
developed on a macronodular cirrhosis, hxmochromatosis which was apparently posttransfusional. Au antigen was not found. Careful questionmg of the patient’s family and all the doctors who had treated her indicated that she had never been given any androgen therapy. accompanied by
a
This observation means that a hepatoma may arise during the course of Fanconi’s anaemia, in the absence of androgen therapy. As in Johnson’s case 3, the hepatoma we report developed on a cirrhosis (probably post-necrotic). The high incidence of leukæmia 9,10 and solid turnouts 11 in patients with Fanconi’s anxmia, and in their families,
is well known. The finding of hepatoma may be a new indication of the " malignant potential " of this disease,12 possibly related to chromosome anomalies.13 Créteil University Medical
School, Department of Internal Medicine and Gastroenterology, Nouvel Hôpital, 94-Villeneuve St. Georges, France.
D. CATTAN P. VESIN J. WAUTIER R. KALIFAT S. MEIGNAN.
CLINDAMYCIN AND PSEUDOMEMBRANOUS COLITIS
SIR The report by Dr Scott and his colleagues
11
and
15-18
have drawn attention to the subsequent correspondence association of severe pseudomembranous colitis with treatment with clindamycin. We have recently seen a patient in whom the presentation was somewhat atypical. A 61-year-old woman started clindamycin 150 mg. 6-hourly and cloxacillin 500 mg. 6-hourly on March 7, 1974, for a superficial skin infection. On March 12 a total hip replacement was performed, and the immediate postoperative course was uneventful. On March 23 the patient complained of sudden onset of diarrhoea, nausea, vomiting, right-sided abdominal pain, and pyrexia, which soon settled with conservative treatment. The antibiotics were discontinued. The diarrhoea (about 3 loose stools a day) was adequately controlled with a kaolin preparation until April 8 when the patient became shocked with gross abdominal distension. Laparotomy and total colectomy with ileostomy was
performed. The bowel showed the characteristic naked-eye mucosal pseudomembranous colitis affecting the whole of the dilated colon and rectal stump, the terminal ileum being spared. Histological examination of the membranous plaque appearance of
confirmed the macroscopic diagnosis, and there was partial and full-thickness mucosal necrosis and patchy necrosis of the muscularis propria with intermuscular haemorrhage. There was thrombosis of the submucosal vessels and paracolic veins.
The case is unusual in that, although the diarrhoea started while the patient was receiving clindamycin, the symptoms were not severe and were readily controlled. It was not until 16 days after cessation of antibiotic therapy that the severe acute symptoms appeared. Perhaps in cases with a similar presentation not only should the present 9. Garriga, J., Crosby, N. H. Blood, 1959, 14, 1008. 10. Dosik, H., Hsu, L. Y., Todaroi, G. J., Lee, S. L., Kirschorn, K., Selirio, E. S. ibid. 1970, 36, 341. 11. Swift, M. R. Nature, 1971, 230, 370. 12. Fanconi G. Personal communication. 13. Schroeder, T. M., Anschutz, F., Knopp, A. Humangenetik, 1964 1, 194. 14. Scott, A. J., Nicholson, G. I., Kerr, A. R. Lancet, 1973, ii, 1232. 15. Sissons, J. G. P., Boulton-Jones, J. M., Peters, D. K. ibid. Feb. 2, 1974, p. 172. 16. Stroehlein, J. R., Hoffman, H. N., Sedlack, R. E., Newcomber A. D. ibid. Feb. 9, 1974, p. 221. 17. Temperley, J. M. ibid. 18. Sneddon, J. ibid.