325 This alarming frequency of side-effects with levamisole forced us to suspend the trial in December, 1977. Before this study was undertaken 53 patients (18 malignant melanoma, 17 hypernephroma, 5 breast cancer, 6 Hodgkin’s disease, 4 malignant teratoma, 1 with lung cancer, 1 gastric cancer, and 1 ovarian cancer) received levamisole in a similar manner for periods ranging from one month to two years. The incidence of side-effects in this group of patients was similar to those reported in other series, and hxmatological disturbances, other than a transient eosinophilia in a patient with hypernephroma, were not observed. We have attributed to levamisole symptom relief in two pa1 tients with advanced Hodgkin’s disease. Like Dr Teerenhovi and others we feel that the frequency of side-effects from levamisole is an important consideration and treatment of neoplastic diseases with this drug should be limited to very carefully selected patients on an individual basis. on our trial was presented to the Breast Trials Review Meeting, held at Heathrow on Feb. 3, 1978, and organised by the Coordinating Committee for Clinical Trials of the Treatment of Human Breast Cancer in Britain and Ireland.
A report
S. RETSAS R. H. PHILLIPS I. W. F. HANHAM K. A. NEWTON
Department of Radiotherapy and Medical Oncology, Westminster Hospital, London SW1P 2AP
CLOFIBRATE AND THE LIVER
.
HISTOPATHOLOGY OF THE LIVER* BEFORE AND AFTER THERAPY WITH CLOFIBRATE 1.5
5 g/day
graded
=(0) no fatty degeneration, (1) mild-to-moderate fatty degeneration, (2) distinct fatty degeneration, (3) severe fatty degeneration and (4) fatty liver. In conclusion, there is some tendency to decreased fatty liver infiltration and no hint of liver damage (by light microscopy) after three months’ clofibrate treatment. Medizinische Klinik II, Klinikum Grosshadern, Universität München, 8000 München 70, West Germany
P. SCHWANDT
Pathologische Institüt, Stadtkrankenhaus, Kassel
O. KLINGE
Institüt für Medizinische Dokumentation, Statistik und Datenverarb., Universität Heidelberg
H. IMMICH
SIR,-A temporary increase of transaminases is a frequent accompaniment of clofibrate treatment for hyperlipoproteinxmia. In
rat
liver ultrastructural
changes2-4
and alterations of
activities,4-’ metabolites and A.D.P.A.T.P. ratio after clofibrate feeding have been reported. Hanefeld et al. reported decreased liver glycogen and manganese content as well as an increase in mitochondria and smooth endoplasmic reticulum in liver-biopsy specimens of clofibric-acid treated patients with hyperlipoproteinaemia. Since this seems to be the only published biopsy evidence for an influence of clofibrate on the .human liver we would like to report a multicentre study on this subject. 40 hyperlipoproteinsemic patients having given their informed consent, had liver biopsies done before and after three months of clofibrate treatment (1-3 g/day in 27,0-55 g/day in 13). Liver tissue was examined by light microscopy by enzyme
of us under "blind" conditions. The results in respect of fatty infiltration are given in the table for the 1.5g/day group. No significant histological changes were seen in the 13 patients on 0.5gclofibrate per day. 17 of 27 patients on 1.5g clofibrate showed distinct fatty degeneration (grade 2) before therapy. 6 of these patients showed histological improvement, 3 deteriorated, and 8 remained unchanged after three months on clofibrate. In respect of other histological criteria there were no differences between patients on 0.5 5 g and 1.5 5 g. Of the 40 patients, 26 showed single-cell necroses; 6 of these remained unchanged at follow-up biopsy, 6 had some more necrosis, but 14 had none after therapy. The same tendency was seen for slight local activity of the mesenchyma, initially present in 32 livers, diminishing in 15 and slightly increasing in 10. Discrete intrahepatic cholestasis was observed 6 times before therapy but only twice at follow-up. Portal fibrosis (12 cases) and siderosis (24) were not influenced by therapy.
SERUM-AMYLASE ISOENZYME PATTERN AFTER PANCREATECTOMY
SIR,-A raised serum-amylase after
surgery isusually indicating postoperative pancreatitis,’-3 even when the patient has no signs or symptoms of pancreatitis. Studies of amylase isoenzyme patterns suggest that increased
accepted
as
one
1. Phillips, R. H., Retsas, S., Newton, K. A. Br. med. J. 1977, i, 1447. 2. Best, M., Duncan, C. J. Lab. clin. Med. 1964, 64, 634. 3. Svoboda, D., Azarnoff, D. J. Cell Biol. 1966, 40, 442. 4. Gear, A., Albert, A., Bednarek, J. J. biol. Chem. 1974, 249, 6495. 5. Hess, R., Staäubli, W., Riess, W. Nature, 1965, 208, 856. 6. Cederbaum, A., Madhayan, T., Rubin, E., Biochem. Pharmac. 1976, 25, 1825.
7. Wilkening, J., Schwandt, P. Horm. Metab. Res. 1977, 8. Hanefeld, M. Dt. Gesundh Wesen 1977, 32, 2267.
9, 132.
Fig. 1-Serum-amylase-activity
after total pancreatectomy.
amylase activity after an operation, even upper-abdominal surgery, may not always derive from the pancreas. However, the mechanism remains unknown. We have monitored changes in serum-amylase isoenzyme patterns after total pancreatectomy, Perryman, R. G., Hoerr, S. O. Am. J.Surg. 1954, 88, 417. Ponka, J. L., Lamdrum, S. E., Chaikof, L. Archs Surg. 1961, 83, 475. 3. White, T. T. Morgan, A., Hopton, D.Am. J.Surg. 1970, 120, 132. 4. Maeda, M. Jap. J. Gastrœnterol. (inthepress). 1. 2.
A report
S. RETSAS R. H. PHILLIPS I. W. F. HANHAM K. A. NEWTON
Department of Radiotherapy and Medical Oncology, Westminster Hospital, London SW1P 2AP
CLOFIBRATE AND THE LIVER
.
HISTOPATHOLOGY OF THE LIVER* BEFORE AND AFTER THERAPY WITH CLOFIBRATE 1.5
5 g/day
graded
=(0) no fatty degeneration, (1) mild-to-moderate fatty degeneration, (2) distinct fatty degeneration, (3) severe fatty degeneration and (4) fatty liver. In conclusion, there is some tendency to decreased fatty liver infiltration and no hint of liver damage (by light microscopy) after three months’ clofibrate treatment. Medizinische Klinik II, Klinikum Grosshadern, Universität München, 8000 München 70, West Germany
P. SCHWANDT
Pathologische Institüt, Stadtkrankenhaus, Kassel
O. KLINGE
Institüt für Medizinische Dokumentation, Statistik und Datenverarb., Universität Heidelberg
H. IMMICH
SIR,-A temporary increase of transaminases is a frequent accompaniment of clofibrate treatment for hyperlipoproteinxmia. In
rat
liver ultrastructural
changes2-4
and alterations of
activities,4-’ metabolites and A.D.P.A.T.P. ratio after clofibrate feeding have been reported. Hanefeld et al. reported decreased liver glycogen and manganese content as well as an increase in mitochondria and smooth endoplasmic reticulum in liver-biopsy specimens of clofibric-acid treated patients with hyperlipoproteinaemia. Since this seems to be the only published biopsy evidence for an influence of clofibrate on the .human liver we would like to report a multicentre study on this subject. 40 hyperlipoproteinsemic patients having given their informed consent, had liver biopsies done before and after three months of clofibrate treatment (1-3 g/day in 27,0-55 g/day in 13). Liver tissue was examined by light microscopy by enzyme
of us under "blind" conditions. The results in respect of fatty infiltration are given in the table for the 1.5g/day group. No significant histological changes were seen in the 13 patients on 0.5gclofibrate per day. 17 of 27 patients on 1.5g clofibrate showed distinct fatty degeneration (grade 2) before therapy. 6 of these patients showed histological improvement, 3 deteriorated, and 8 remained unchanged after three months on clofibrate. In respect of other histological criteria there were no differences between patients on 0.5 5 g and 1.5 5 g. Of the 40 patients, 26 showed single-cell necroses; 6 of these remained unchanged at follow-up biopsy, 6 had some more necrosis, but 14 had none after therapy. The same tendency was seen for slight local activity of the mesenchyma, initially present in 32 livers, diminishing in 15 and slightly increasing in 10. Discrete intrahepatic cholestasis was observed 6 times before therapy but only twice at follow-up. Portal fibrosis (12 cases) and siderosis (24) were not influenced by therapy.
SERUM-AMYLASE ISOENZYME PATTERN AFTER PANCREATECTOMY
SIR,-A raised serum-amylase after
surgery isusually indicating postoperative pancreatitis,’-3 even when the patient has no signs or symptoms of pancreatitis. Studies of amylase isoenzyme patterns suggest that increased
accepted
as
one
1. Phillips, R. H., Retsas, S., Newton, K. A. Br. med. J. 1977, i, 1447. 2. Best, M., Duncan, C. J. Lab. clin. Med. 1964, 64, 634. 3. Svoboda, D., Azarnoff, D. J. Cell Biol. 1966, 40, 442. 4. Gear, A., Albert, A., Bednarek, J. J. biol. Chem. 1974, 249, 6495. 5. Hess, R., Staäubli, W., Riess, W. Nature, 1965, 208, 856. 6. Cederbaum, A., Madhayan, T., Rubin, E., Biochem. Pharmac. 1976, 25, 1825.
7. Wilkening, J., Schwandt, P. Horm. Metab. Res. 1977, 8. Hanefeld, M. Dt. Gesundh Wesen 1977, 32, 2267.
9, 132.
Fig. 1-Serum-amylase-activity
after total pancreatectomy.
amylase activity after an operation, even upper-abdominal surgery, may not always derive from the pancreas. However, the mechanism remains unknown. We have monitored changes in serum-amylase isoenzyme patterns after total pancreatectomy, Perryman, R. G., Hoerr, S. O. Am. J.Surg. 1954, 88, 417. Ponka, J. L., Lamdrum, S. E., Chaikof, L. Archs Surg. 1961, 83, 475. 3. White, T. T. Morgan, A., Hopton, D.Am. J.Surg. 1970, 120, 132. 4. Maeda, M. Jap. J. Gastrœnterol. (inthepress). 1. 2.
