770 remarkable feature was the uniformity of the contamination: clearly the activity has been deposited from the air. All surfaces were decontaminated. The fan in the fume cupboard of the laboratory had been out of operation over the two-month period. Subsequently as many operations as possible were done in the fume cupboard, even though it would not normally be considered necessary to work in a fume cupboard at the activities involved. The fan was run continuously to promote air changes. Over the next three months no surface contamination was detected, except on working surfaces.
positive for HBeAg and 45.5% are positive for HBeAb. Owing to vagaries of the immune response and the sensitivity of the techniques used, it is not clear whether the remaining 50% have been exposed to e antigen.
Radiochemical Laboratory, Department of Chemistry, University of Dundee, Dundee DD1 4HN
Department of Medical Microbiology, University College,
I. S. MCLINTOCK
Department of Obstetrics and Gynæcology, University of Dundee
J.
We thank Dr J. Wallace, of the Glasgow and West of Scotland Regional Transfusion Centre, for his help. This work was supported by a grant from the Distillers Company Limited.
University Department Royal Infirmary, Glasgow, G4 0SF
M. J. PARKER R. B. GOUDIE A. G. SHATTOCK
Belfield, Dublin
L. YOUNG
DISULFIRAM-INDUCED MYOCARDIAL AND SKELETAL-MUSCLE DEGENERATION IN RATS
CEREBRAL BLOOD-FLOW IN POLYCYTHÆMIA
SIR,—The paper by Dr Thomas and his colleagues (July 23, 161) may be relevant to patients with hypoxic lung disease and secondary polycythsemia. Such patients frequently have cerebral symptoms which are usually attributed to the low
p.
. p a02 and raised Paco2. After isovolumetric venesection (e.g., with dextran 40) there is usually a clinical improvement in these symptoms but no concomitant change in blood gases or respiratory-function tests.’ When the packed cell volume rises the benefits of increased oxygen carriage are outweighed by the exponential increase in blood viscosity and the resultant reduction in blood-flow.2 It is unlikely that altered renal perfusion plays a role in this improvement-indeed venesection should probably be done only on patients with a normal blood-urea.3 Much of the apparently subjective improvement reported by patients with polycythaemic chronic obstructive lung disease after isovolumetric venesection may result from increased cerebral blood-flow. Brook General London SE18
of Pathology,
Hospital, DAVID HONEYBOURNE
SIR,-Disulfiram has been used as a fungicide and rubber chemical and for the treatment of alcoholism. Like many other thiocarbamates it is biotransformed to carbon disulphide.1,2 Many of the toxicological properties of disulfiram, such as its neurotoxicity, may be attributed to this biotransformation product. Animal studies on carbon disulphide,3,4 disulfiram,s and thiram6 have described muscle incoordination, ataxia, and tremor as well as paralysis, suggesting that the neurotoxic effects of carbon disulphide may lead to muscle impairment. We have looked for morphological effects of disulfiram on skeletal muscle and myocardium. 30 Sprague-Dawley rats of each sex were given disulfiram
120, mg/kg body-weight daily by
gavage
as a
microsuspension
in ’Methocel 65 Hg’ water solution. The same number of control animals were given the vehicle alone. Five animals of each
1. Johnston, C. D., Prickett, C. S. Biochim. biophys. Acta. 1952, 9, 219. Fischer, R., Brantner, H. ArzneimittelForsch., 1967, 17, 1461. Lewey, F. H. J. ind. Hyg. Toxicol., 1941, 23, 415 Wronska-Nofer, T., Stetkiewicz, J., Szendzikowski, S. Int. Arch. Arbeitsmed. 1973, 31, 123. 5. Child, G. P. Crump, M. Acta pharmac. toxicol., 1952, 8, 305. 6. Lee, C. G., Peters, P. J. Envir. Hlth Perspect. 1976, 17, 35.
2. 3. 4.
INCIDENCE OF HBe ANTIGEN AND HBe ANTIBODY IN BLOOD-DONORS
SIR,-In South-West Scotland 0-2% of healthy blood-
hepatitis-B surface (HBs) antigensemia as assessed by radioimmunoassay. 88 HBsAg-positive plasmas from blooddonors were examined for the presence of e antigen (HBeAg) and anti-e antibody (HBeAb) by an immunodiffusion technique. Several plasmas, mainly high-titre HBeAb-positive, produced multiple lines and for this reason results were considered positive only when they produced a line of confluence with standard HBeAg and HBeAb. All negative samples were concentrated fourfold by ultrafiltration and tested against a panel of e and anti-e positive plasmas. This was found, greatly enhancing the sensitivity of HBeAg detection. The sensitivity ofHBeAb detection was 29% greater: donors have
These findings demonstrate that approximately 50% of HBjAg carriers have evidence of e-antigen exposure: 3-4% are Harrison, B. Gregory, R., Clark, T., Scott, G. Br. med. J. 1971, iv, 713. Dintenfass, L., Read, J. Lancet, 1968, i, 570. 3. Honeybourne, D. Br. med. J. 1977, i, 52.
1. 2.
Fig. 1—Section firam 120
of rat
myocardmm after treatment with disul-
mg/kg/day
for 14
myocardial degeneration. (H. & E.-, x 250.)
days showing acute-subacute
771
Fig. 2-Mesenteric lymph-node after treatment with disulfiram 120 mg/kg/day for 14 days showing heemosiderosis. (Perl’s method for ferric iron; reduced to 2/3 of x 160.) killed after 7 days of exposure, and the rest were killed after 14 days. Frozen sections of skeletal and cardiac muscle, liver, kidneys, and tongue were stained with scarletred. Embedded sections were stained with haematoxylin and eosin and Perl’s method for ferric iron. In all rats given disulfiram a focal acute-subacute myocardial degeneration was observed, characterised by swelling, disintegration, and fatty infiltration of the muscle fibres. Invasion by macrophages in degenerated areas was also seen (fig. 1). The degenerative changes occurred in animals exposed for 7 days as well as in those exposed for 2 weeks. In biceps and triceps brachii, quadriceps, and gastrocnemius muscles and in the tongue a qualitatively and quantitatively similar focal degeneration was observed in all exposed animals at both 7 and 14 sex were
days. The liver showed a slight fatty infiltration of hepatic cells in four out of ten animals after 7 days. At 14 days fatty infiltration was observed in sixteen out of twenty animals. These and varied between moderate All rats showed moderate or severe haemosiderosis in the mesenteric lymph-nodes after 14 days (fig. 2). The muscle degeneration observed was not associated with disturbances of behaviour or locomotion. It might, however, be followed by impairment of muscle function in animals exposed to higher doses or for a longer time to thiocarbamates or to carbon disulphide. The myocardial degeneration we found has not been described previously and might be associated with similar observations in dogs3 exposed to carbon disulphide or in rats’ subject to concomitant exposure to noradrenaline (norepinephrine) or phenobarbitone with carbon disulphide. Thiram produced muscle degeneration of the gastrocnemius in rats,’ and an increased risk of myocardial infarction has been associated with occupational exposure to carbon disulphide.8
changes were mainly peripheral and
severe.
S. EKVÄRN AB
Kabi, S-10425 Stockholm, Sweden
M. JÖNSSON N. G.
LINDQUIST
National Board of Occupational Safety and Health, S-100 26 Stockholm
B. HOLMBERG
National Veterinary Institute, S-104 05 Stockholm
T. KRONEVI
MECHANICAL METHODS AGAINST DEEP-VEIN THROMBOSIS
SiR,—Your editorial (Sept. 3, p. 490) ends on a note of caupractical limitations of mechanical methods of
tion about the 7. 8
Chandra, S V., Butter, W. H., Magos, L. Explmol. Pharmac. 1972, 17, 249. Hernberg, S., Tolonen, M., Nurminen, M. Scand. J. Work envir. Hlth, 1976. 2, 27.
preventing postoperative deep-vein thrombosis. In our experience these problems have been exaggerated. For the past six months we have been using below-knee graduated static compression stockings’ and pneumatic leggings2 in patients undergoing laparotomy, apart from those in lithotomy or lateral positions, who are fitted with electrical calf stimulators.3.4 In addition dextran-70s is given during and after the operation. The use of dextran-70 has resulted in one case of transient circulatory overloading, but the mechanical methods have been completely free of complications. We have encountered no problems in the application of compression leggings or calf stimulators. The time taken is no longer than that required to apply and connect the diathermy pad. The additional work is negligible, and there have been no storage problems. At other hospitals the routine application of compression leggings has been similarly problem-free. These have been used in about 4000 patients at St. Helier Hospital, Carshalton, among whom none has had signs of pulmonary embolism within three weeks of surgical operation.6 Recent reports of haemorrhage in patients receiving low-dose heparin 7,S may stimulate surgeons to look again at mechanical methods; our experience has dispelled any misgivings about difficulties or added work-load. DAVID NEGUS SYLVIA QUAILE DAVID WILMHURST Operating Theatres, VERNON ROBINSON Lewisham Hospital, London SE13 6LH RAY SMITH
TREATMENT OF EROSIVE LICHEN PLANUS OF THE ORAL MUCOSA WITH DEPOT STEROIDS
SIR,-The oral ulceration associated with erosive lichen causes considerable and sometimes protracted discomfort. The response to local applications of corticosteroids is variable probably because it is difficult to keep the drug in contact with the mucosal lesion for a sufficient time. Sometimes systemic administration of corticosteroids is resorted to. Intralesional steroid therapy does have a use in dermatology,9 and erosive lichen planus of the mouth has been treated with triamcinolone acetonide in a few patients’"’’’ Five patients with persistent ulceration of the oral mucosa were treated. Lichen planus was diagnosed clinically and confirmed histologically. The areas of ulceration varied from the tongue to the labial and buccal mucosa and the ulceration had not responded to conventional topical steroid therapy. One patient had had ulcers on the lateral margin of the tongue for about 3 months. An aqueous suspension containing methylprednisolone acetate 40 mg/ml (’Depo-Medrone’) was used and 0.5-1.0 ml was injected submucosally. The white suspension tended to leak from the injection site but this was overcome by inserting the needle at least 10 mm from the ulcerated area. The response was encouraging, improvement usually being evident by 48 h; and in four cases the lesions healed within a week. One patient required a second injection of 0-5ml after
planus
Holford, C. P. Br. J. Surg. 1976, 63, 157. Hills, N. H., Pflug, J. J., Jeyasingh, K., Boardman, L., Calnan, J. S. Br. med. J. 1972, i,131. 3. Doran, F. S. A., White, H. M., Drury, M. Br. J. Surg. 1970, 57, 20. 4. Browse, N. L., Negus, D. Br. med. J. 1970, iii, 615. 5. Kline, K., Hughes, L. E., Campbell, H., Williams, A., Zlosnick, J., Leach,
1. 2.
K. G. ibid. 1975, ii, 109.
Wells, B. W. Personal communication. Gruber, U. F., Duchert, F., Fridrich, R., Torhorst, J., Rem, J. Lancet, 1977, i, 207. 8. Britton, B. J., Finch, D. R. A., Gill, P. G., Kettlewell, M. G. W., Morris, P. J. ibid. 1977, ii, 604. 9. Verbov, J. Br. J. Derm. 1976, 94, suppl. 15, p. 51. 10. Taylor, A. Dent. Practit. 1966, 17, 56. 11. Sleeper, H. R. Yale J. Biol. Med. 1967, 40, 164. 6. 7.
positive for HBeAg and 45.5% are positive for HBeAb. Owing to vagaries of the immune response and the sensitivity of the techniques used, it is not clear whether the remaining 50% have been exposed to e antigen.
Radiochemical Laboratory, Department of Chemistry, University of Dundee, Dundee DD1 4HN
Department of Medical Microbiology, University College,
I. S. MCLINTOCK
Department of Obstetrics and Gynæcology, University of Dundee
J.
We thank Dr J. Wallace, of the Glasgow and West of Scotland Regional Transfusion Centre, for his help. This work was supported by a grant from the Distillers Company Limited.
University Department Royal Infirmary, Glasgow, G4 0SF
M. J. PARKER R. B. GOUDIE A. G. SHATTOCK
Belfield, Dublin
L. YOUNG
DISULFIRAM-INDUCED MYOCARDIAL AND SKELETAL-MUSCLE DEGENERATION IN RATS
CEREBRAL BLOOD-FLOW IN POLYCYTHÆMIA
SIR,—The paper by Dr Thomas and his colleagues (July 23, 161) may be relevant to patients with hypoxic lung disease and secondary polycythsemia. Such patients frequently have cerebral symptoms which are usually attributed to the low
p.
. p a02 and raised Paco2. After isovolumetric venesection (e.g., with dextran 40) there is usually a clinical improvement in these symptoms but no concomitant change in blood gases or respiratory-function tests.’ When the packed cell volume rises the benefits of increased oxygen carriage are outweighed by the exponential increase in blood viscosity and the resultant reduction in blood-flow.2 It is unlikely that altered renal perfusion plays a role in this improvement-indeed venesection should probably be done only on patients with a normal blood-urea.3 Much of the apparently subjective improvement reported by patients with polycythaemic chronic obstructive lung disease after isovolumetric venesection may result from increased cerebral blood-flow. Brook General London SE18
of Pathology,
Hospital, DAVID HONEYBOURNE
SIR,-Disulfiram has been used as a fungicide and rubber chemical and for the treatment of alcoholism. Like many other thiocarbamates it is biotransformed to carbon disulphide.1,2 Many of the toxicological properties of disulfiram, such as its neurotoxicity, may be attributed to this biotransformation product. Animal studies on carbon disulphide,3,4 disulfiram,s and thiram6 have described muscle incoordination, ataxia, and tremor as well as paralysis, suggesting that the neurotoxic effects of carbon disulphide may lead to muscle impairment. We have looked for morphological effects of disulfiram on skeletal muscle and myocardium. 30 Sprague-Dawley rats of each sex were given disulfiram
120, mg/kg body-weight daily by
gavage
as a
microsuspension
in ’Methocel 65 Hg’ water solution. The same number of control animals were given the vehicle alone. Five animals of each
1. Johnston, C. D., Prickett, C. S. Biochim. biophys. Acta. 1952, 9, 219. Fischer, R., Brantner, H. ArzneimittelForsch., 1967, 17, 1461. Lewey, F. H. J. ind. Hyg. Toxicol., 1941, 23, 415 Wronska-Nofer, T., Stetkiewicz, J., Szendzikowski, S. Int. Arch. Arbeitsmed. 1973, 31, 123. 5. Child, G. P. Crump, M. Acta pharmac. toxicol., 1952, 8, 305. 6. Lee, C. G., Peters, P. J. Envir. Hlth Perspect. 1976, 17, 35.
2. 3. 4.
INCIDENCE OF HBe ANTIGEN AND HBe ANTIBODY IN BLOOD-DONORS
SIR,-In South-West Scotland 0-2% of healthy blood-
hepatitis-B surface (HBs) antigensemia as assessed by radioimmunoassay. 88 HBsAg-positive plasmas from blooddonors were examined for the presence of e antigen (HBeAg) and anti-e antibody (HBeAb) by an immunodiffusion technique. Several plasmas, mainly high-titre HBeAb-positive, produced multiple lines and for this reason results were considered positive only when they produced a line of confluence with standard HBeAg and HBeAb. All negative samples were concentrated fourfold by ultrafiltration and tested against a panel of e and anti-e positive plasmas. This was found, greatly enhancing the sensitivity of HBeAg detection. The sensitivity ofHBeAb detection was 29% greater: donors have
These findings demonstrate that approximately 50% of HBjAg carriers have evidence of e-antigen exposure: 3-4% are Harrison, B. Gregory, R., Clark, T., Scott, G. Br. med. J. 1971, iv, 713. Dintenfass, L., Read, J. Lancet, 1968, i, 570. 3. Honeybourne, D. Br. med. J. 1977, i, 52.
1. 2.
Fig. 1—Section firam 120
of rat
myocardmm after treatment with disul-
mg/kg/day
for 14
myocardial degeneration. (H. & E.-, x 250.)
days showing acute-subacute
771
Fig. 2-Mesenteric lymph-node after treatment with disulfiram 120 mg/kg/day for 14 days showing heemosiderosis. (Perl’s method for ferric iron; reduced to 2/3 of x 160.) killed after 7 days of exposure, and the rest were killed after 14 days. Frozen sections of skeletal and cardiac muscle, liver, kidneys, and tongue were stained with scarletred. Embedded sections were stained with haematoxylin and eosin and Perl’s method for ferric iron. In all rats given disulfiram a focal acute-subacute myocardial degeneration was observed, characterised by swelling, disintegration, and fatty infiltration of the muscle fibres. Invasion by macrophages in degenerated areas was also seen (fig. 1). The degenerative changes occurred in animals exposed for 7 days as well as in those exposed for 2 weeks. In biceps and triceps brachii, quadriceps, and gastrocnemius muscles and in the tongue a qualitatively and quantitatively similar focal degeneration was observed in all exposed animals at both 7 and 14 sex were
days. The liver showed a slight fatty infiltration of hepatic cells in four out of ten animals after 7 days. At 14 days fatty infiltration was observed in sixteen out of twenty animals. These and varied between moderate All rats showed moderate or severe haemosiderosis in the mesenteric lymph-nodes after 14 days (fig. 2). The muscle degeneration observed was not associated with disturbances of behaviour or locomotion. It might, however, be followed by impairment of muscle function in animals exposed to higher doses or for a longer time to thiocarbamates or to carbon disulphide. The myocardial degeneration we found has not been described previously and might be associated with similar observations in dogs3 exposed to carbon disulphide or in rats’ subject to concomitant exposure to noradrenaline (norepinephrine) or phenobarbitone with carbon disulphide. Thiram produced muscle degeneration of the gastrocnemius in rats,’ and an increased risk of myocardial infarction has been associated with occupational exposure to carbon disulphide.8
changes were mainly peripheral and
severe.
S. EKVÄRN AB
Kabi, S-10425 Stockholm, Sweden
M. JÖNSSON N. G.
LINDQUIST
National Board of Occupational Safety and Health, S-100 26 Stockholm
B. HOLMBERG
National Veterinary Institute, S-104 05 Stockholm
T. KRONEVI
MECHANICAL METHODS AGAINST DEEP-VEIN THROMBOSIS
SiR,—Your editorial (Sept. 3, p. 490) ends on a note of caupractical limitations of mechanical methods of
tion about the 7. 8
Chandra, S V., Butter, W. H., Magos, L. Explmol. Pharmac. 1972, 17, 249. Hernberg, S., Tolonen, M., Nurminen, M. Scand. J. Work envir. Hlth, 1976. 2, 27.
preventing postoperative deep-vein thrombosis. In our experience these problems have been exaggerated. For the past six months we have been using below-knee graduated static compression stockings’ and pneumatic leggings2 in patients undergoing laparotomy, apart from those in lithotomy or lateral positions, who are fitted with electrical calf stimulators.3.4 In addition dextran-70s is given during and after the operation. The use of dextran-70 has resulted in one case of transient circulatory overloading, but the mechanical methods have been completely free of complications. We have encountered no problems in the application of compression leggings or calf stimulators. The time taken is no longer than that required to apply and connect the diathermy pad. The additional work is negligible, and there have been no storage problems. At other hospitals the routine application of compression leggings has been similarly problem-free. These have been used in about 4000 patients at St. Helier Hospital, Carshalton, among whom none has had signs of pulmonary embolism within three weeks of surgical operation.6 Recent reports of haemorrhage in patients receiving low-dose heparin 7,S may stimulate surgeons to look again at mechanical methods; our experience has dispelled any misgivings about difficulties or added work-load. DAVID NEGUS SYLVIA QUAILE DAVID WILMHURST Operating Theatres, VERNON ROBINSON Lewisham Hospital, London SE13 6LH RAY SMITH
TREATMENT OF EROSIVE LICHEN PLANUS OF THE ORAL MUCOSA WITH DEPOT STEROIDS
SIR,-The oral ulceration associated with erosive lichen causes considerable and sometimes protracted discomfort. The response to local applications of corticosteroids is variable probably because it is difficult to keep the drug in contact with the mucosal lesion for a sufficient time. Sometimes systemic administration of corticosteroids is resorted to. Intralesional steroid therapy does have a use in dermatology,9 and erosive lichen planus of the mouth has been treated with triamcinolone acetonide in a few patients’"’’’ Five patients with persistent ulceration of the oral mucosa were treated. Lichen planus was diagnosed clinically and confirmed histologically. The areas of ulceration varied from the tongue to the labial and buccal mucosa and the ulceration had not responded to conventional topical steroid therapy. One patient had had ulcers on the lateral margin of the tongue for about 3 months. An aqueous suspension containing methylprednisolone acetate 40 mg/ml (’Depo-Medrone’) was used and 0.5-1.0 ml was injected submucosally. The white suspension tended to leak from the injection site but this was overcome by inserting the needle at least 10 mm from the ulcerated area. The response was encouraging, improvement usually being evident by 48 h; and in four cases the lesions healed within a week. One patient required a second injection of 0-5ml after
planus
Holford, C. P. Br. J. Surg. 1976, 63, 157. Hills, N. H., Pflug, J. J., Jeyasingh, K., Boardman, L., Calnan, J. S. Br. med. J. 1972, i,131. 3. Doran, F. S. A., White, H. M., Drury, M. Br. J. Surg. 1970, 57, 20. 4. Browse, N. L., Negus, D. Br. med. J. 1970, iii, 615. 5. Kline, K., Hughes, L. E., Campbell, H., Williams, A., Zlosnick, J., Leach,
1. 2.
K. G. ibid. 1975, ii, 109.
Wells, B. W. Personal communication. Gruber, U. F., Duchert, F., Fridrich, R., Torhorst, J., Rem, J. Lancet, 1977, i, 207. 8. Britton, B. J., Finch, D. R. A., Gill, P. G., Kettlewell, M. G. W., Morris, P. J. ibid. 1977, ii, 604. 9. Verbov, J. Br. J. Derm. 1976, 94, suppl. 15, p. 51. 10. Taylor, A. Dent. Practit. 1966, 17, 56. 11. Sleeper, H. R. Yale J. Biol. Med. 1967, 40, 164. 6. 7.
