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ANALGESIC NEPHROPATHY IN WEST GERMANY
210 CLINICAL FEATURES AND FUCOSYLATED AFP LEVELS IN FIVE PATIENTS REPORTED
-
i
*Ages shown
at in
first
hospital
admission
.1
(A)
in
J
May,
1979
I
(Case 1), February,
I
1978
(Case 2), October,
I
(Case 3), September,
1975
L
(Case 4), and May,
1982
(Case 5)
Second
hospnat admission
column B.
CHANGE IN FUCOSYLATION OF &agr;-FETOPROTEIN ON MALIGNANT TRANSFORMATION OF LIVER CELLS
SIR,-A fucosylated variant of a-fetoprotein (AFP) seems to be a good marker for hepatocellular carcinoma (HCC) at an early stage1,2 and should be helpful in the follow-up of patients with benign liver diseases (BLD) when serum AFP concentrations rise.We describe here five patients in whom the degree of fucosylation of serum AFP altered in association with HCC after a long history of chronic liver disease. For example, a 66-year-old woman (case 1) was admitted on May 30, 1979, because of an increased serum AFP (530 ng/ml) which might have been related to the onset of HCC. Selective coeliac arteriography, however, revealed no evidence of HCC. Histopathological examination of a specimen obtained by peritoneoscopy-guided needle biopsy indicated early cirrhosis. Her serum AFP then fell gradually below 20 ng/ml and she was discharged. Serum AFP rose again (390 ng/ml) in Feb 2, 1984, 41/2 years after the first rise. Arteriography revealed an oval-shaped HCC (4-7x2-77 cm) in the right lobe. The percentage of the fucosylated variant of AFP was 7% at her first hospital admission, when early cirrhosis was diagnosed, cirrhosis, but 89% when she had clear evidence of HCC (table). Similar clinical cases which showed the distinct change in a glycosylation pattern of AFP are also included in this table. These data suggest that the liver fucosyltransferase activity responsible for the production of the fucosylated variant of AFP rises in association with HCC. The mechanism for this increase is not known, but could be activation of fucosyltransferase or enhanced expression of the gene of this enzyme upon malignant transformation of hepatocytes.
Third
I
1977
Division,
Department of Internal Medicine, Nugata University School of Medicine, Nugata 951, Japan; and Department of Biochemistry, Tohoku University School of Medicine, Sendai
YUTAKA AOYAGI MAMORU ISEMURA YASUFUMI SUZUKI CHUICHI SEKINE KENJI SOGA TOSHIHIKO OZAKI FUMIHIRO ICHIDA
statistics released by the German pharmaceutical industry for 198344 indicate total sales of 2 - 9 x 109 analgesic tablets (or 48 per person per year) and average consumption of 1 -3gphenacetin. This phenacetin consumption is lower than that given in earlier reports of consumption in Australia (40 g) and Switzerland (22 g) but is higher than the 1 g or less recorded in Scandinavia.5,6 In West Germany replacement of phenacetin by paracetamol (acetaminophen) in combination drugs led to a fall in the number of phenacetin mixtures between 1977 and 1984 from 112 to 58; the number of paracetamol mixtures increased from 116 to 154.7.7 However, it is not yet known whether paracetamol is less nephrotoxic than phenacetin,and 54 000 kg of phenacetin was dispensed by prescription in 1983.4In West Germany since 1981 packages of analgesics containing phenacetin have had to carry a warning but there are no other statutory controls. There are 17 000 patients with end-stage renal disease in West Germany.9 If about 15% of all dialysis patients have analgesic nephropathy there must be roughly 2500 patients with terminal analgesic nephropathy. If there are the same number of predialysis patients with analgesic nephropathy, as experience in outpatient clinics indicates, the total number of patients in West Germany with clinically manifest analgesic nephropathy would be 5000. About 600 000 individuals (1% of the general population) are analgesic abusers.l0 So analgesic abuse carries a 1% risk of clinically manifest analgesic nephropathy. Even so, analgesic nephropathy remains a serious problem in Western countries, where analgesic abuse may still be more frequent than is generally accepted.
and Institute of Preventive
and Social Medicine, Bremen 1. Pommer
W, Broda M, Moizahn M On the prevalence of analgesic nephropathy
2.
Republic of Germany and West Berlin. In: Analgesic nephropathy Epidemiology-pathology-prevention symposium (University of Antwerp, 1984) Schwarz A, Pommer W, Kühn-Freitag G, Keller F, Molzahn M, Offermann G Merkmale der terminalen Analgetika-Nephropathie. Schweiz Med Wschr 1985; 115:
790-95. 3. Schwarz A, Faber 4.
1 Aoyagi Y,
ANALGESIC NEPHROPATHY IN WEST GERMANY
SiR,-In the 1950s Swiss investigators drew attention to analgesic abuse and analgesic nephropathy but in some centres analgesic abuse remains a considerable cause of renal disease. A 1983 survey of forty-nine dialysis centres’ in Germany showed that analgesic nephropathy accounted for 13% of dialysis cases (a prevalence similar to that reported for new dialysis patients by the European Dialysis and Transplant Association in 1982). However, frequencies ranged from 0% to 50%, and analgesic nephropathy was the most frequently diagnosed primary disease in the 144 patients in in our dialysis centre z Roughly 10% of female Berlin are taking more than one analgesic mixture daily, and sales
outpatients
in the
Federal
U, Borner K, Keller F, Offermann G, Molzahn M. Reliability of analgesic users. Lancet 1984; ii: 1163-64. Der Pharmazeutische Markt in der BRD. Institut fur Medizinische Statistik, Frankfurt am Main, 1983. Duggin GG. Mechanisms in the development of analgesic nephropathy. Kidney Int 1980; 18: 553-61.
drug history
Suzuki Y, Isemura M, et al. Differential reactivity of alpha-fetoprotein with lectins and evaluation of its usefulness in the diagnosis of hepatocellular carcinoma Gann 1984; 75: 809-15 2 Aoyagi Y, Isemura M, Yosizawa Z, et al. Fucosylation of serum alpha-fetoprotein in patients with primary hepatocellular carcinoma. Biochim Biophys Acta 1985; 830: 217-23 3. Aoyagi Y, Isemura M, Suzuki Y, et al. Fucosylated alpha-fetoprotein as marker of early hepatocellular carcinoma Lancet 1985; ii: 1353-54.
A. SCHWARZ U. FABER G. GLAESKE F. KELLER G. OFFERMANN
Department of Medicine, Klinikum Steglitz, Free University of Berlin, 1000 Berlin 45, West Germany;
5
in
6. Nordic Statistics
on Medicine 1978-1980. Uppsala, 1982. 7. Pharmszeutische Stoffliste. Arzneimittelbüro der Bundesvereinigung Deutscher Apothekenverbände. 1977 and 1984. 8 Nanra RS. Analgesic nephropathy: Aetiology, clinical syndrome and clinico-pathologic correlations in Australia. Kidney Int 1978; 13: 79-92. 9. Schoeppe W. Indikation, Methoden und Ergebnisse der intermittierenden Dauerdialysebehandlung. Internist 1983; 24: 494-99 10. Schwarz A, Faber U, Glaeske G, et al. Daten zu Analgetika-Konsum und AnalgetikaWes 1985; 47: 298-300. Nephropathie in der Bundesrepublik.
Öff Gesundh
CHLORACNE IN FIREFIGHTERS
SIR,-Chloracne (halogen acne) is a disorder of the pilosebaceous glands which is persistent, refractory to standard acne treatments, and may be associated with systemic toxicity. Known causes include polyhalogenated naphthalenes, biphenyls, dibenzofurans, and dibenzodioxins. Lately, tetrachloroazoxybenzene and tetrachlorobenzene have been implicated too.Clinically and histologically the differentiation of chloracne from acne vulgaris (especially in mild cases in isolated individuals) can be impossible. 1,2
-
i
*Ages shown
at in
first
hospital
admission
.1
(A)
in
J
May,
1979
I
(Case 1), February,
I
1978
(Case 2), October,
I
(Case 3), September,
1975
L
(Case 4), and May,
1982
(Case 5)
Second
hospnat admission
column B.
CHANGE IN FUCOSYLATION OF &agr;-FETOPROTEIN ON MALIGNANT TRANSFORMATION OF LIVER CELLS
SIR,-A fucosylated variant of a-fetoprotein (AFP) seems to be a good marker for hepatocellular carcinoma (HCC) at an early stage1,2 and should be helpful in the follow-up of patients with benign liver diseases (BLD) when serum AFP concentrations rise.We describe here five patients in whom the degree of fucosylation of serum AFP altered in association with HCC after a long history of chronic liver disease. For example, a 66-year-old woman (case 1) was admitted on May 30, 1979, because of an increased serum AFP (530 ng/ml) which might have been related to the onset of HCC. Selective coeliac arteriography, however, revealed no evidence of HCC. Histopathological examination of a specimen obtained by peritoneoscopy-guided needle biopsy indicated early cirrhosis. Her serum AFP then fell gradually below 20 ng/ml and she was discharged. Serum AFP rose again (390 ng/ml) in Feb 2, 1984, 41/2 years after the first rise. Arteriography revealed an oval-shaped HCC (4-7x2-77 cm) in the right lobe. The percentage of the fucosylated variant of AFP was 7% at her first hospital admission, when early cirrhosis was diagnosed, cirrhosis, but 89% when she had clear evidence of HCC (table). Similar clinical cases which showed the distinct change in a glycosylation pattern of AFP are also included in this table. These data suggest that the liver fucosyltransferase activity responsible for the production of the fucosylated variant of AFP rises in association with HCC. The mechanism for this increase is not known, but could be activation of fucosyltransferase or enhanced expression of the gene of this enzyme upon malignant transformation of hepatocytes.
Third
I
1977
Division,
Department of Internal Medicine, Nugata University School of Medicine, Nugata 951, Japan; and Department of Biochemistry, Tohoku University School of Medicine, Sendai
YUTAKA AOYAGI MAMORU ISEMURA YASUFUMI SUZUKI CHUICHI SEKINE KENJI SOGA TOSHIHIKO OZAKI FUMIHIRO ICHIDA
statistics released by the German pharmaceutical industry for 198344 indicate total sales of 2 - 9 x 109 analgesic tablets (or 48 per person per year) and average consumption of 1 -3gphenacetin. This phenacetin consumption is lower than that given in earlier reports of consumption in Australia (40 g) and Switzerland (22 g) but is higher than the 1 g or less recorded in Scandinavia.5,6 In West Germany replacement of phenacetin by paracetamol (acetaminophen) in combination drugs led to a fall in the number of phenacetin mixtures between 1977 and 1984 from 112 to 58; the number of paracetamol mixtures increased from 116 to 154.7.7 However, it is not yet known whether paracetamol is less nephrotoxic than phenacetin,and 54 000 kg of phenacetin was dispensed by prescription in 1983.4In West Germany since 1981 packages of analgesics containing phenacetin have had to carry a warning but there are no other statutory controls. There are 17 000 patients with end-stage renal disease in West Germany.9 If about 15% of all dialysis patients have analgesic nephropathy there must be roughly 2500 patients with terminal analgesic nephropathy. If there are the same number of predialysis patients with analgesic nephropathy, as experience in outpatient clinics indicates, the total number of patients in West Germany with clinically manifest analgesic nephropathy would be 5000. About 600 000 individuals (1% of the general population) are analgesic abusers.l0 So analgesic abuse carries a 1% risk of clinically manifest analgesic nephropathy. Even so, analgesic nephropathy remains a serious problem in Western countries, where analgesic abuse may still be more frequent than is generally accepted.
and Institute of Preventive
and Social Medicine, Bremen 1. Pommer
W, Broda M, Moizahn M On the prevalence of analgesic nephropathy
2.
Republic of Germany and West Berlin. In: Analgesic nephropathy Epidemiology-pathology-prevention symposium (University of Antwerp, 1984) Schwarz A, Pommer W, Kühn-Freitag G, Keller F, Molzahn M, Offermann G Merkmale der terminalen Analgetika-Nephropathie. Schweiz Med Wschr 1985; 115:
790-95. 3. Schwarz A, Faber 4.
1 Aoyagi Y,
ANALGESIC NEPHROPATHY IN WEST GERMANY
SiR,-In the 1950s Swiss investigators drew attention to analgesic abuse and analgesic nephropathy but in some centres analgesic abuse remains a considerable cause of renal disease. A 1983 survey of forty-nine dialysis centres’ in Germany showed that analgesic nephropathy accounted for 13% of dialysis cases (a prevalence similar to that reported for new dialysis patients by the European Dialysis and Transplant Association in 1982). However, frequencies ranged from 0% to 50%, and analgesic nephropathy was the most frequently diagnosed primary disease in the 144 patients in in our dialysis centre z Roughly 10% of female Berlin are taking more than one analgesic mixture daily, and sales
outpatients
in the
Federal
U, Borner K, Keller F, Offermann G, Molzahn M. Reliability of analgesic users. Lancet 1984; ii: 1163-64. Der Pharmazeutische Markt in der BRD. Institut fur Medizinische Statistik, Frankfurt am Main, 1983. Duggin GG. Mechanisms in the development of analgesic nephropathy. Kidney Int 1980; 18: 553-61.
drug history
Suzuki Y, Isemura M, et al. Differential reactivity of alpha-fetoprotein with lectins and evaluation of its usefulness in the diagnosis of hepatocellular carcinoma Gann 1984; 75: 809-15 2 Aoyagi Y, Isemura M, Yosizawa Z, et al. Fucosylation of serum alpha-fetoprotein in patients with primary hepatocellular carcinoma. Biochim Biophys Acta 1985; 830: 217-23 3. Aoyagi Y, Isemura M, Suzuki Y, et al. Fucosylated alpha-fetoprotein as marker of early hepatocellular carcinoma Lancet 1985; ii: 1353-54.
A. SCHWARZ U. FABER G. GLAESKE F. KELLER G. OFFERMANN
Department of Medicine, Klinikum Steglitz, Free University of Berlin, 1000 Berlin 45, West Germany;
5
in
6. Nordic Statistics
on Medicine 1978-1980. Uppsala, 1982. 7. Pharmszeutische Stoffliste. Arzneimittelbüro der Bundesvereinigung Deutscher Apothekenverbände. 1977 and 1984. 8 Nanra RS. Analgesic nephropathy: Aetiology, clinical syndrome and clinico-pathologic correlations in Australia. Kidney Int 1978; 13: 79-92. 9. Schoeppe W. Indikation, Methoden und Ergebnisse der intermittierenden Dauerdialysebehandlung. Internist 1983; 24: 494-99 10. Schwarz A, Faber U, Glaeske G, et al. Daten zu Analgetika-Konsum und AnalgetikaWes 1985; 47: 298-300. Nephropathie in der Bundesrepublik.
Öff Gesundh
CHLORACNE IN FIREFIGHTERS
SIR,-Chloracne (halogen acne) is a disorder of the pilosebaceous glands which is persistent, refractory to standard acne treatments, and may be associated with systemic toxicity. Known causes include polyhalogenated naphthalenes, biphenyls, dibenzofurans, and dibenzodioxins. Lately, tetrachloroazoxybenzene and tetrachlorobenzene have been implicated too.Clinically and histologically the differentiation of chloracne from acne vulgaris (especially in mild cases in isolated individuals) can be impossible. 1,2