45 The reason for this remains uncertain, but the appearance of psychotic symptoms after sudden withdrawal may indicate that baclofen influences mechanisms involved in various types of psychosis. It is therefore tempting to suggest that further clinical trials with baclofen should be carried out in psychiatric disorders.
extrapyramidal signs.
Manglerud Nevrohjem and Department of Neurology, Rikshospitalet, University of Oslo, Oslo, Norway
R. STIEN
SIR,-Dr Skausig and Dr Korsgaard’ describe a parkinsonian patient on levodopa and carbidopa who had hallucinations when also given baclofen. Because the hallucinations were similar to those occurring in this patient on levodopa, they conclude that baclofen affects dopamine metabolism. There is no direct chemical evidence for such an effect in man,2 and hallucinations are a recognised, though rare, side-effect of baclofen in patients with no evidence of an abnormality of dopamine pathways. In addition their patient and ours3 had hallucinations on withdrawal of baclofen; in our patient this was
accompanied by dyskinesia.
An alternative explanation for the hallucinations on withdrawal of baclofen may lie in the evidence of an antagonism between this drug and substance P.4 This putative neurotransmitter has been shown to have an excitatory effect on dopaminergic neurones. Withdrawal of baclofen might therefore abruptly increase the level of activity in dopaminergic pathways. Its use in parkinsonian patients should clearly be closely
supervised. A. J. LEES
Department of Neurological Studies, Middlesex Hospital Medical School, London W1N 8AA
C. R. A. CLARKE M. J. HARRISON
of 70%. It is then possible to transfuse these leucocyte-poor platelet concentrates to immunised patients who can no longer withstand fresh platelets. In such cases, we have observed excellent tolerance and satisfactory management of hxmorrhagic syndromes (provided that the transfusions are repeated every 2 or 3 days). A second useful application of this system of freezing platelets obtained by cytopheresis is the possibility of storing autologous platelets for leukaemia patients.8 The platelets can be used’ subsequently in cases of relapse or bone-marrow aplasia induced by chemotherapy. This reserve of HLA-typed platelets will allow exchanges between centres to solve the difficult transfusion problems met with in immunised thrombocyto-
penic patients. P. HERVE M. MASSE C. COFFE A. PETERS
Laboratoire de Centre
Cryobiologie, Regional de Transfusion Sanguine,
25003 Besançon, France
THERMOPHILIC ACTINOMYCETES IN AIR OF COTTON MILLS
SIR,-Byssinosis is an occupational disease of workers who process certain vegetable fibres, including cotton, flax,lo and soft hemp." Byssinosis is a progressive disease with a variety of respiratory symptoms including acute dyspnoea with cough and chest tightness on one or more days of the working week, usually after a weekend break or other absence. In the early stages the disease is reversible, and symptoms disappear if workers change occupations or work in dust-free parts of a mill. If no such change of occupation is made then the disease progresses over several years resulting in an irreversible obstructive lung condition. The identity and mode of action of causative agent(s) is not established and suggested causes include proteolytic enzymes, certain microbial toxins, polysaccharides, condensed tannins, aromatic and terpenoid compounds, other pigments, and
antigens.’ A lot of work has been done
CRYOPRESERVING HLA-TYPED PLATELETS OBTAINED ON CELL SEPARATORS
SiR,—The importance of a frozen platelet bank in fusion
is
well known. For
a
trans-
year, the Besancon Regional Blood Transfusion Centre has had at its disposal a reserve of glycerol-glucose cryoprotected platelets, stored in liquid nitrogen.6.7 At first, each frozen unit was prepared from a pool of four donors, and for treatment of hxmorrhagic syndromes 3 frozen units (equivalent to 12 units of Fresh platelets) were transfused. In 78% of cases the cryopreserved platelets had immediate haemostatic activity equivalent to that of fresh platelets, but haemorrhagic relapses appeared sooner (on the third day). Given the frequency of immunisation to leucocytes and platelets and the intolerance to or even inefficiency of platelet transfusions in immune patients, we now prefer to freeze platelets obtained from a single HLAtyped donor, using a cell separator (HaEmonetics model 30). Each cytopheresis yields 5 x 1011 to 6x 10’1 platelets. To reduce immunisations in the HLA system and to avoid the harmful effect on platelets of the enzymes liberated by the granulocytes which lyse during the freezing period, we eliminate 85% of the leucocytes by slow centrifugation (800 revolutions over 20 min). With this technique 25% of the platelets are lost in the leucocyte pellet. The final quantity of platelets to be frozen is on average 3 x 10" to 4 x 10" cells with a yield after thawing centre
1. Skausig, O. B.,
now
Korsgaard, S. Lancet, 1977, i,
over one
1258.
2. Walinder, J., Wallin, L., Carlsson, A. New Engl. J. Med. 1977, 296, 452. 3. Lees, AJ., Clarke, C. R. A., Harnson, M. J. Lancet, 1977, i, 858. 4. Saito, K., Konishi, S., Otsuka, M. Brain Res. 1975, 97, 177. 5. Magnusson, T., Carlsson, A., Fisher, G. H. J. neurol. Transmiss. 1976, 38, 89 6. Dayian, G. Rowe, A. W. Cryobiology, 1976,13,1. 7. Herve, P., Masse, M., Kieffer, Y., Carbillet, J. P., Bidet, A., Bosset, Peters, A Revue Fr Transfus. Immuno-Hémat. (in the press).
J. F.,
on
possible
links between
bys-
sinosis and fungi and certain types of eubacteria, 13.14 but bacteria of the order Actinomycetales have received little attention. This is a significant omission because actinomycetes of the genera Thermoactinomyces and Micropolyspora have been implicated in pulmonary allergies such as farmer’s lung, IS mushroom worker’s lung, 16 and bagassosis" which are in some respects similar to byssinosis. We have investigated the actinomycete content in the air of Lancashire cotton spinning mills and the prevalence of byssinosis as determined by Medical Research Council questionnaire. These preliminary studies have shown the presence of substantial numbers of actinomycetes, particularly T. vulgaris 5000-22 000/m3 in the air of cotton mills. T. vulgaris colonies were identified by colony appearance, spore arrangement, and novobiocin resistance. They produced typical phase-bright endospores of the type implicated in farmer’s lung, and were isolated on C.Y.C./tyrosine media, which separates them into melanin+ and melanin- types’8 for the first time in this type
of study. People exposed to Thermoactinomyces spores might well be expected to develop symptoms similar to those of the extrinsic allergic alveolitis of farmer’s lung,’ mushroom worker’s lung,8 Schieffer, C. A., Buchholz, D. H., Aisner J., Wolff, J. H., Wiernik, P. H. Transfusion, 1976, 16, 321. 9. Roach, S. A., Schilling, R. S. F. Br.J. ind. Med. 1960, 17, 1. 10. Bouhuys, A., Van Duyn, J., Van Lennap, H. J. Archs envir. Hlth, 1961, 3, 8.
499. 11. Barbero, A., Flores, R. ibid. 1967, 14, 529. 12. Wakelyn, P. J., Greenblatt, G. A., Brown, D. F.,
Hyg.Ass.J. 1976,37,22. 13. Tuffnell, P. Br. J. ind. Med. 1960, 16, 304. 14. Furness, G., Maitland, H. B. ibid. 1952, 9, 138. 15. Pepys, J., Jenkins, P.A. Thorax, 1965,20,21. 16. Sakula, A. Br. med.J 1967, ii, 708. 17. Lacey, J.J. gen. Microbiol, 1971, 66, 327. 18. Cross, T, Unsworth, B. A. Lancet, 1976,i,959.
Tripp,
V. W. Am. ind.
46
bagassosis. In all three diseases precipitating antibodies specific for T. vulgaris have been detected in patients’ sera. We and
have started to look for such antibodies in the sera of cottonmill workers. The source of thermoactinomycetes could be moist cotton bales which heat up, thereby providing ideal growth conditions for the organisms. If so, it might be feasible to reduce the air level of thermoactinomycete spores by control of storage conditions of baled cotton. Medical School,
University of Manchester, Manchester M 13 9PL
M. G. LOCKWOOD
Department of Biological Sciences, Manchester Polytechnic, Manchester M13 9PL
R. W. ATTWELL
THE GREAT CIRCULATORY PARADOX
SIR,-The use of 12SI-Iabelled fibrinogen to study thrombosis in the coronary arteries is fairly new and it is desirable that the evidence should not become confused at this early stage. Dr Short’s review1 is not innocent in this respect. It is true that our observations on the uptake of radiofibrinogen by coronary thrombus in acute myocardial infarction have led us to a different conclusion from Erhardt et al. But far from being "basically similar" our technique was fundamentally different. Erhardt et al. removed thrombi post mortem from the coronary arteries, divided them into three portions, and measured the radioactivity in a liquid scintillation counter. We identified the site and intensity of radioactivity by autoradiography of serially mounted 2 mm transverse sections throughout the length of the lesions. In this way the thrombus was examined in situ and small portions of radionegative thrombus could be identified. The sections were mounted far enough apart for there to be no contamination by neighbouring radioactive thrombus. Our method of autoradiography of transverse sections is evidently more discriminative in regard to the distribution of radiopositivity and radionegativity along the length of the lesion than are the methods used by Erhardt et al.2 or Moschos et al. on thrombus removed from the coronary arteries or by Erhardt et al.4 in a later study using autoradiography of longitudinal sections of the coronary arteries from 12 cases. In Erhardt’s later study, not referred to in Dr Short’s survey, the finding of radioactivity throughout the length of the lesion where radiofibrinogen had been given within 10 h of the onset in four cases was held, with some reservations, to support the previous conclusions that thrombus was a sequel to infarction. Our own findings give little or no support to this conclusion. Occlusive thrombus of negative or very low radioactivity (i.e., less than a quarter the usual activity of whole blood clot) was found in most occlusive lesions, despite the fact that the onsetto-radiofibrinogen interval was often short (3-12 h) and despite the accumulation of strongly radioactive thrombus at either end of most lesions. In only 6 out of 25 cases-’ (6 out of 32 cases in our later report6) was the lesion radioactive throughout ; of these, 2 had received the radiofibrinogen during unstable angina before myocardial infarction and 4 had had more than one episode of infarction. The message of our observations is based on the relative lack of radioactivity in the central occlusive part of most thrombotic lesions, indicating that occlusion by thrombus was completed early in the course of the fatal illness-possibly before myocardial infarction. This message is in no way disturbed by the observations of Moschos et 1. Short, D. Lancet, 1977, i, 1244. Erhardt, L. R., Lundman, T., Mellsted, T. H. ibid. 1973, i, 387. Moschos, C. B., Oldewurtel, H. A., Haider, B., Regan, T. J. Circulation,
2. 3.
some measure of support from them. Far from undermining the evidence derived from radiofibrinogen studies in man, as Dr Short suggests, the experimental work of Moschos et al.3 undermines only the conclusion that radioactivity in a thrombus necessarily implies its formation after the time of radiofibrinogen administration. In other words, this work offers alternative explanation for the radioactivity of some of the occlusive thrombi reported by Erhardt et al. and for some of the instances in our series. Whether the radioactivity at the ends of many of our lesions resulted from thrombus formation after radiofibrinogen or from infiltration of thrombus already formed are questions that have little consequence for the radionegativity of the central occlusive portion of the thrombus which we have demonstrated, and upon which our conclusions depend. There remains the conflict between the high frequency in our series of low levels of radioactivity in the centre of naturally occuring occlusive thrombus in the diseased coronary arteries of man and the diffuse radiopositivity regularly found by Moschos et al. in experimental thrombi in previously normal coronary arteries of the dog. We do not know whether this difference depends on structural characters of the thrombi or on the methods of examination or on both. In this important controversy on the role of coronary occlusion in myocardial infarction it has been customary to apply due-perhaps even excessive--caution before extrapolating the results of animal experiment to man. It would be logical that this caution should also be applied to radiofibrinogen studies.
al.,’ and could indeed gain
University Department of Materia Medica, Stobhill General Hospital, Glasgow, and West of Scotland Department of Clinical Physics and Bioengineering
W. F. M. FULTON
D. J. SUMNER
DEGOS’ DISEASE TREATED WITH PLATELETSUPPRESSIVE DRUGS
SIR,-Treatment of malignant atrophic papulosis (Degos’ disease) is disappointing. This is a report of a patient succesfully treated with platelet-suppressive drugs. 1.2 The patient is a 31-year-old male who has had a skin eruption since February, 1976, consisting of erythematous papules, gradually developing umbilication, and, finally, atrophic porcelain-white centres with an erythematous border. Spells of dizziness and short-lasting visual disturbances occurred before the appearance of new lesions. Ophthalmological and neurological examination was normal, and no signs of gastrointestinal involvement was found. Light microscopy of fresh lesions showed infarction of the skin with newly thrombosed vessels in the corium. Electronmicroscopy of skin-biopsy material revealed tubular structures resembling paramyxovirus located in the cytoplasm of the endothelial cells; however, no membrane-bound particles could be demonstrated.3 Electron-dense granular material was noted in’some fibroblasts interpreted as phagocytosed material, possibly melanin. No other evidence suggesting viral infection was found and all laboratory tests were normal except for increased platelet aggregation with maximum aggregation with adenosine diphosphate 0-75 µmol/l and noradrenaline (norepinephrine) 0-ng/m!.4 Platelet-suppressive drugs were prescribed-acetylsalicylic acid 500 mg twice daily and dipyridamole (’Persantin’) 50 mg three times daily. One new skin lesion appeared during the first month of treatment but during the next 8 months no fresh cutaneous lesions showed up, and the dizziness disappeared. The platelet-aggregation tests are now normal. The cause and pathogenesis of this rare, often fatal disease
1976,54,653. 4. Erhardt, L. R., Unge, G., Boman, G. Am. Heart J. 1976, 91, 592. 5. Fulton, W. F. M., Sumner, D. J. Proc. 7th Eur. Congr. Cardiol. 1976. 6. Fulton, W. F. M., Sumner, D. J. Am.J. Cardiol. 1977, 39, 322.
Amsterdam,
1. Weiss, H. J. Am. Heart.J. 1976,92,86. 2. Harker, L. A. Ser. Hœmat. 1976,8,105. 3. Müller, S. A., Landry, M.Arch. Derm. 1976,112,357. 4. Gormsen, J., Andersen, L. A., Nielsen, J. D. Ugeskr. Lœg. (in the press).