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BASIC SCIENCE IN CLINICAL RESEARCH
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of autonomic changes during sleep, particularly in the paradoxical phase. Furthermore, Dr. Paul to their implications drew attention Turner (London) with many After treatment for hypnotis therapy. in which reduce time paradoxical spent hypnotic drugs sleep, there is a rebound period with an increase in the proportion of time spent in this sleep stage.1 Perhaps this is associated with an increased risk of nocturnal angina and hypertensive episodes. tance
BARBITURATE COMA AND BLISTERS
SINCE one of the earliest reports by Villaret,2in 1932, there have been a number of accounts of bullous lesions in barbiturate poisoning. Lately these lesions have attracted much more interest-perhaps a reflection of the increasing incidence of acts of self-poisoning. In comatose patients the characteristic blisters may be strong pointers to intoxication by hypnotic agents. Clinical reports of barbiturate intoxication have described tense bullae in areas of erythema where the skin has previously been exposed to pressure, but the lesions are not necessarily found in maximum pressure areas-common sites are the fingers, inner aspect of the knee, and over the malleoli. The bulloc have always been in patients previously unconscious, they usually appeared within twenty-four hours of ingestion of the drug, and they were seen in 4-7% of patients. 3-5 The histology was described in detail by Adebahr,6 who reported a 40% incidence of blisters in a series of necropsies in 300 cases of barbiturate poisoning. He noted striking epidermal necrosis, with little change in the dermis except that the sweat-glands were severely involved and the blisters seemed to begin around the epidermal part of the sweat-ducts. Subsequent histological examination of lesions in comatose patients has confirmed this.7-9 There is still considerable controversy about the method of formation of these interesting bullae.1Oo Some workers believe they result from central effects in coma, some say that they are purely due to pressure, and the title of one paper 9 suggests that they are due to trauma, though the text provides very little evidence of this and indicates hypoxia as a major factor. Coma and pressure seem unlikely primary causes, since bullae are not seen in all forms of drug-induced coma. The lesions also develop much more rapidly than pressure sores and are not necessarily over sites of maximum pressure. Histology shows predominantly epidermal and sweat-gland necrosis with little dermal change, and this too is not suggestive of a pressure effect. The view has been put forward that the effect may be a direct one, since barbiturates are known to interfere with epidermal metabolism; that the sweat-gland epithelium 1. Oswald, I., Priest, R. G. Br. med. J. 1965, ii, 1093. 2. Villaret, M., Bith, H., Desoille, M. Paris méd. 1932, 2, 340. 3. Holten, C. Acta derm. vener., Stockh. 1952, suppl. 29, 162. 4. Lowther, C. P. Scott. med. J. 1959, 4, 163. 5. Beveridge, G. W., Lawson, A. A. H. Br. med. J. 1965, i, 835. 6. Adebahr, G. Der Landarzt, 1963, 30, 1302. 7. Leavell, U. W. Archs Derm. 1969, 100, 218. 8. Brehmer-Anderson, E., Pederson, N. B. Acta derm. vener., Stockh. 1969, 49, 157. 9. Mandy, S., Ackerman, A. B. J. Am. med. Ass. 1970, 213, 253. 10. Beveridge, G. W. in Acute Barbiturate Poisoning (edited by H. J. S. Matthew); p. 129. Amsterdam, 1971.
may be
involved; and that the sweat-glands would be
especially susceptible since they excrete barbiturate and increase the concentration locally. Pressure probably predisposes to the lesions by interfering with the circulation and increasing hypoxia at a time when the epidermis is at risk. This hypothesis is supported by Naylor’s observation 11 that, of a number of sedative drugs, barbiturates have the greatest tendency to reduce oxygen consumption in the skin. Though barbiturates are the commonest cause of the lesions, similar bullx have been seen in a few cases of carbon-monoxide 12 and amitriptyline 13 poisoning and isolated cases of meprobamate, methadone, glutethimide,14 and nitrazepam 15 overdosage.
BASIC SCIENCE IN CLINICAL RESEARCH
NEARLY every important advance in clinical medicine this century has come from application of the basic sciences. Yet nowadays few research clinicians can hope to keep pace with progress even in biochemistry, physiology, and pharmacology. The alternative is to work in close association with scientists expert in the relevant subjects; but this may present difficulties. Basic scientists have in the past had a poor deal in clinical research-lack of medical qualifications often prevented them reaching the top-and now some science departments regard clinical work as not quite respectable. Indeed, the basic scientist may feel that if he lets his interests stray in the clinical direction he risks not only treatment as a second-class citizen by his medical associates but also ostracism by his science colleagues. This separation, which is increasing, will have to be counteracted if clinical research is to achieve its full potential-and this means greater clinical orientation in the basic-science departments of the medical schools. The young scientist will have to be shown that he can take an interest in clinical problems without risk to his future. Too often a. young man has worked alongside a clinician for a few years, has made an important contribution because of his special knowledge, and has then had to revert to non-clinical work to safeguard his position in the
departmental hierarchy. This week the Wellcome Trust announces a linked fellowship scheme which is an attempt to bridge the gap for the scientist and still preserve his future (see p. 757). In essence, the Trust says: When we provide a fellowship for a basic scientist to work alongside a clinician we will require the head of the basic-science department to be a co-sponsor and to look after the young man’s future as he would for one of his own young men ". This could be an important step, but it will require substantial efforts from the clinicians and scientists if it is to be successful. Perhaps through the initial care of a linked fellow, clinicians and scientists will themselves forge links which will not only benefit clinical research but also encourage the basic sciences to turn to the problems of man. "
11. 12. 13. 14. 15.
Naylor, P. D. F., Evans, N. T. S. Br. J. Derm. 1970, 82, 600. Meigs, J. W., Hughes, J. P. M. Archs ind. Mycol. 1952, 6, 344. Noble, J., Matthew, H. Clin. Toxicol. 1969, 2/4, 403. Sorensen, B. F. Dan. med. Bull. 1963, 10, 130. Ridley, C. M. Br. med. J. 1971, iii, 28.
of autonomic changes during sleep, particularly in the paradoxical phase. Furthermore, Dr. Paul to their implications drew attention Turner (London) with many After treatment for hypnotis therapy. in which reduce time paradoxical spent hypnotic drugs sleep, there is a rebound period with an increase in the proportion of time spent in this sleep stage.1 Perhaps this is associated with an increased risk of nocturnal angina and hypertensive episodes. tance
BARBITURATE COMA AND BLISTERS
SINCE one of the earliest reports by Villaret,2in 1932, there have been a number of accounts of bullous lesions in barbiturate poisoning. Lately these lesions have attracted much more interest-perhaps a reflection of the increasing incidence of acts of self-poisoning. In comatose patients the characteristic blisters may be strong pointers to intoxication by hypnotic agents. Clinical reports of barbiturate intoxication have described tense bullae in areas of erythema where the skin has previously been exposed to pressure, but the lesions are not necessarily found in maximum pressure areas-common sites are the fingers, inner aspect of the knee, and over the malleoli. The bulloc have always been in patients previously unconscious, they usually appeared within twenty-four hours of ingestion of the drug, and they were seen in 4-7% of patients. 3-5 The histology was described in detail by Adebahr,6 who reported a 40% incidence of blisters in a series of necropsies in 300 cases of barbiturate poisoning. He noted striking epidermal necrosis, with little change in the dermis except that the sweat-glands were severely involved and the blisters seemed to begin around the epidermal part of the sweat-ducts. Subsequent histological examination of lesions in comatose patients has confirmed this.7-9 There is still considerable controversy about the method of formation of these interesting bullae.1Oo Some workers believe they result from central effects in coma, some say that they are purely due to pressure, and the title of one paper 9 suggests that they are due to trauma, though the text provides very little evidence of this and indicates hypoxia as a major factor. Coma and pressure seem unlikely primary causes, since bullae are not seen in all forms of drug-induced coma. The lesions also develop much more rapidly than pressure sores and are not necessarily over sites of maximum pressure. Histology shows predominantly epidermal and sweat-gland necrosis with little dermal change, and this too is not suggestive of a pressure effect. The view has been put forward that the effect may be a direct one, since barbiturates are known to interfere with epidermal metabolism; that the sweat-gland epithelium 1. Oswald, I., Priest, R. G. Br. med. J. 1965, ii, 1093. 2. Villaret, M., Bith, H., Desoille, M. Paris méd. 1932, 2, 340. 3. Holten, C. Acta derm. vener., Stockh. 1952, suppl. 29, 162. 4. Lowther, C. P. Scott. med. J. 1959, 4, 163. 5. Beveridge, G. W., Lawson, A. A. H. Br. med. J. 1965, i, 835. 6. Adebahr, G. Der Landarzt, 1963, 30, 1302. 7. Leavell, U. W. Archs Derm. 1969, 100, 218. 8. Brehmer-Anderson, E., Pederson, N. B. Acta derm. vener., Stockh. 1969, 49, 157. 9. Mandy, S., Ackerman, A. B. J. Am. med. Ass. 1970, 213, 253. 10. Beveridge, G. W. in Acute Barbiturate Poisoning (edited by H. J. S. Matthew); p. 129. Amsterdam, 1971.
may be
involved; and that the sweat-glands would be
especially susceptible since they excrete barbiturate and increase the concentration locally. Pressure probably predisposes to the lesions by interfering with the circulation and increasing hypoxia at a time when the epidermis is at risk. This hypothesis is supported by Naylor’s observation 11 that, of a number of sedative drugs, barbiturates have the greatest tendency to reduce oxygen consumption in the skin. Though barbiturates are the commonest cause of the lesions, similar bullx have been seen in a few cases of carbon-monoxide 12 and amitriptyline 13 poisoning and isolated cases of meprobamate, methadone, glutethimide,14 and nitrazepam 15 overdosage.
BASIC SCIENCE IN CLINICAL RESEARCH
NEARLY every important advance in clinical medicine this century has come from application of the basic sciences. Yet nowadays few research clinicians can hope to keep pace with progress even in biochemistry, physiology, and pharmacology. The alternative is to work in close association with scientists expert in the relevant subjects; but this may present difficulties. Basic scientists have in the past had a poor deal in clinical research-lack of medical qualifications often prevented them reaching the top-and now some science departments regard clinical work as not quite respectable. Indeed, the basic scientist may feel that if he lets his interests stray in the clinical direction he risks not only treatment as a second-class citizen by his medical associates but also ostracism by his science colleagues. This separation, which is increasing, will have to be counteracted if clinical research is to achieve its full potential-and this means greater clinical orientation in the basic-science departments of the medical schools. The young scientist will have to be shown that he can take an interest in clinical problems without risk to his future. Too often a. young man has worked alongside a clinician for a few years, has made an important contribution because of his special knowledge, and has then had to revert to non-clinical work to safeguard his position in the
departmental hierarchy. This week the Wellcome Trust announces a linked fellowship scheme which is an attempt to bridge the gap for the scientist and still preserve his future (see p. 757). In essence, the Trust says: When we provide a fellowship for a basic scientist to work alongside a clinician we will require the head of the basic-science department to be a co-sponsor and to look after the young man’s future as he would for one of his own young men ". This could be an important step, but it will require substantial efforts from the clinicians and scientists if it is to be successful. Perhaps through the initial care of a linked fellow, clinicians and scientists will themselves forge links which will not only benefit clinical research but also encourage the basic sciences to turn to the problems of man. "
11. 12. 13. 14. 15.
Naylor, P. D. F., Evans, N. T. S. Br. J. Derm. 1970, 82, 600. Meigs, J. W., Hughes, J. P. M. Archs ind. Mycol. 1952, 6, 344. Noble, J., Matthew, H. Clin. Toxicol. 1969, 2/4, 403. Sorensen, B. F. Dan. med. Bull. 1963, 10, 130. Ridley, C. M. Br. med. J. 1971, iii, 28.