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Peripheral Neuropathies
1246 have been reported, 1-4 and clearly we must examine the facts surrounding this dangerous complication of antibiotic therapy. Oxytetracycline and aureomycin are the antibiotics2 especially implicated, but FAIRLIE and KENDALL
similar
cases
observed the same type of enteritis in patients given combined course of penicillin and dihydrostreptomycin by intramuscular injection. Obviously there is need for discretion in the choice of antibiotic, to prevent postoperative infection or to treat an established infection, where the patient’s general condition is much reduced either by severe or long-continued infection or by such states as malnutrition and chronic alcoholism. For example, weighing risk against likely gain, the powerful bactericidal effect of streptomycin and penicillin is essential for the successful treatment of endocarditis caused by Streptococcus fcccalis ;; since the infection is not otherwise curable the hazard of this particularly powerful combination is justified. But it is doubtful whether such a combination can justifiably be given to prevent postoperative infection. The " broad-spectrum antibiotics-aureomycin, oxytetracycline, and chloramphenicol-have obvious attractions as prophylactics in that they are given by mouth and protect against so many organisms, particularly those of the intestinal tract. But these drugs rather often provoke some gastro-intestinal disturbance, and it is a mistake to suppose that the symptoms are always either mild or transient. At the recent Washington symposium on antibiotics5 the discovery of a new antibiotic, tetracycline (’ Achromycin ’), was announced. The chief advantage claimed for it is that it causes much less nausea, vomiting, and diarrhoea than either of
a
"
its
near
relatives, aureomycin (chlortetracycline)
oxytetracycline,
with which it shares many
or
properties.
If this is confirmed the new drug will indeed be welcome. Meanwhile in choosing prophylactics it should not be forgotten that succinylsulphathiazole by mouth and penicillin by injection provide good cover with little risk, and that moderate dosage over a short period is likely to be effective. Altogether it seems that much current practice is based on unduly pessimistic estimates of the risk of sepsis complicating operations, with the result that patients are being needlessly exposed to real dangers by over-insurance against complications which are improbable and which can readily be controlled by prompt treatment with antibiotics. There can be no substitutes for a sound aseptic technique and for watchful care during convalescence ; these will contribute far more to the safety and welfare of patients than a carefree enthusiBefore asm for hearty doses of the latest antibiotic. the era of sulphonamides and antibiotics sepsis had become a relatively rare complication of deliberate
operations. We normally
terms with our almost ungracious and certainly naive to disturb their balance suddenly in preparing for a surgical operation. We cannot by giving known antibiotics eliminate all forms of living micro-organism from the intestinal tract, and we must
intestinal
-live
on
bacteria, and it
peaceful
seems
1. Minn. Med. 1953, 36, 63. 2. Fairlie, C. W., Kendall, R. E. J. Amer. med. Ass. 3. Terplan, K. Amer. J. Path. 1953, 29, 595. 4. Janbon, L., Bertrand, J., Roux, J., Salvaing, J. Méd., Paris, 1952, 136, 59. 5. See Brit. Med. J. Nov. 7, 1953, p. 1043.
1953, 153, 90. Bull. Acad.
that suppression of the species sensitive -to the chosen antibiotic will favour proliferation of those which are insensitive. We still know little of the complicated influences governing the ecology of the bacterial population of the intestine, but common sense suggests that it may be best for the patient to weather a surgical crisis in company with the organisms with which he has come to terms. Perhaps staphylococci are not the sole cause of the enterocolitis reported by Dr. GARDNER and others, but many coagulase-positive staphylococci produce enterotoxin and may give rise to sharp outbreaks of food-poisoning.
expect
Owing to our own activities, staphylococci in hospitals are now largely resistant to the antibiotics in general use, and it has-been suggested that erythromycin, as it becomes available here, might be reserved for cases of staphylococcal enteritis. Such restraint, however, would not be in keeping with the general popularity of new antibiotics, and in any event erythromycinresistant staphylococci appear very readily. In the Washington symposium,5 LEPPER referred to a hospital in which after five months’ use of erythromycin the carrier-rate of highly resistant strains reached 75%. The remedy seems to involve, firstly, educating ourselves to use antibiotics sparingly, taking full advantage of other means of preventing surgical sepsis, and, secondly, undertaking careful and critical studies of the normal intestinal bacteria and of the influences, including antibiotics, which determine important changes in this richly varied population.
Peripheral Neuropathies FEW nosological problems can be more difficult than that of the peripheral neuropathies. Rational classification is difficult because of the wide clinical variations and the complex pathological and biochemical findings.6 Accordingly in treatment the to has been tendency apply any remedy for which success has been claimed, regardless of the type of neural disorder. Clinically the disturbance may be peripheral, in the nerve-roots, in the spinal cord, in the brain, or in the cranial nerves, but this variation only suggests varying susceptibility of the neuronal groups. Pathologically, too, the findings vary enormously. For instance, in the Guillain-Barre syndrome (infective neuronitis, infec-
polyneuritis, polyradiculoneuritis), SCHEINKER7 impressed by the pronounced swelling of nervefibres in the spinal roots and cord tracts and in the cranial and peripheral nerves ; while LOWENBERG and FOSTERdescribed degeneration of the myelin in the peripheral nerves, spinal cord, ganglia, and tive was
brain-stem. FORSTER et al.,9 on the other hand, found that the central nervous system was not materially affected. Such different pathological findings clearly reflect the differences in the clinical picture ; they are no doubt due partly to differences in the temporal evolution of the disorder. Biochemically a few features are now clearly defined. JOINER et aI.l0 showed that neuropathy due to 6. See Elkington, J. H. C., Thompson, R. H. S., Matthews, W. B. Proc. R. Soc. Med. 1952, 45, 661. 7. Scheinker, I. M. J. Neuropath. 1949, 8, 184. 8. Lowenberg, K., Foster, D. B. Arch. Neural. Psychiat., Chicago, 1945, 53, 185. 9. Forster, F. M., Brown, M., Merritt, H. H. New Engl. J. Med.
1941, 225, 51.
10. Joiner, C. 73, 431.
L., MeArdle, B., Thompson,
R. H. S.
Brain, 1950,
1247
vitamin-:B1 deficiency is associated with inhibition of system. Other workers have suggested an allergic the pyruvate-oxidase enzyme system ; and THOMPSON6 basis, emphasising the histological picture of oedema of the neural tissues leading to secondary myelin out that has pointed abnormally high blood-pyruvate with neuroin found not be levels may degeneration. These days such a hypothesis leads only patients but also with associated vitamin-13l deficiency inevitably to a trial of cortisone or corticotrophin pathy to due toxic with those in lewisite, (A.C.T.H.). Among others, BLOOD et al.12 and NEwEY neuropathies are believed These substances and LUBIN13 have reported dramatic improvement in metals. other or arsenic, the Guillain-Barré syndrome after administration of to disturb the pyruvate-oxidase system by their attrac25 mg. of corticotrophin intravenously over a period tion for the sulphhydryl groups of the enzyme In the of 8 hours each day for 5-10 days. Discontinuation deficiency neuropathies (possibly proteins. it is some diabetic reasonable to of treatment was followed by relapse, but this was forms) including administer vitamin Bi, and in the toxic neuropathies successfully countered by a further course. In this dimercaprol (BAL),which is believed to restore enzyme issue Dr. LIVERSEDGE and Dr. LEATHER report a good equilibrium. In the majority of neuropathies, however, response in a patient with polyneuritis associated there ’is no clear indication that either vitamin-B1 with periarteritis nodosa. This association is well or intoxication is at work-and this seems it seems and deficiency recognised, possible that both disorders to apply also to the rare neurological affections be due to tissue may hypersensitivity which may be associated with porphyria and with carcinoma. or due to affection of the vasa neuronal primarily nervorum. Apparently allergy may play an important The most common form is the Guilliain-Barre syndrome, and it is chiefly in this group that the part in the Guillain-Barré syndrome ; the sensitising various remedies have been assessed. VAN HAGEN agent is still unknown, but this syndrome almost 11 BAKER have described their in and invariably follows some minor infection. Furthermore experiences the polyneuritis associated with measles, mumps, 23 cases treated with a combination of vitamin B1 and dimercaprol. They found that about half of diphtheria, and even porphyria might also be explained Though the evidence is still these patients seemed to " show improvement," and by this hypothesis. the concluded that this improvement indicated that the day imperfect, may be approaching when neurocan be treated more rationally. was itself due to disturbance of the pathies syndrome enzyme 11. Van Hagen, K.
12. Blood, A., Locke, W., Carabasi, R. Ibid, 1953, 152, 139. 13. Newey, J. A., Lubin, R. I. Ibid, p. 137.
O., Baker, R. N. J. Amer. med. Ass. 1953.
151, 1465.
TEETHING-POWDERS
Annotations CLINICAL RESEARCH BOARD THE Medical Research Council announces this week the membership of the Clinical Research Board, set up in accordance with the white-paper on Clinical Research in Relation to the National Health Service.’ The board, appointed for three years after consultation with the Ministry of Health and the Department of Health for Scotland, has the following members : Sir GEOFFREY JEFFERSON, F.R.S., emeritus professor of neurosurgery, University of Manchester (chairman) ; Prof. DUGALD BAIRD, midwifery department, University of Aberdeen ; Sir HENRY COHEN, department of medicine, University of Liverpool; Prof. E. C. DODDS, F.R.S., Courtauld Institute of Biochemistry, Middlesex Hospital, London ; Sir JAMEs LEARMONTH, department of surgery, University of Edinburgh ; Prof. A. J. LEWIS, Institute of Psychiatry, Maudsley Hospital, London ; Prof. G. W. PICKERING, medical unit, St. Mary’s Hospital, London ; Prof. R. PLATT, department of medicine, University of Manchester ; Sir JAMES PATERSON Ross, surgical unit, St. Bartholomew’s Hospital, London; Sir JAMES SPENCE, department of child health, King’s College, Newcastle upon Tyne ; and Prof. B. W. WINDEYER, Meyerstein Institute of Radiotherapy, Middlesex Hospital, London. The chief medical officers of the Ministry of Health, the Department of Health for Scotland, and the Ministry of Health and Local Government in Northern Ireland will be assessors to the board, and the secretary of the Medical Research Council will attend all meetings. Dr. F. J. C. Herrald, a senior medical officer on the council’s headquarters staff, will act as secretary.
The board will be concerned with promoting whatever clinical research needs to be organised on a national basis. It will aim to ensure that all fields of inquiry are adequately covered, and will collect, collate, and distribute information in order to reduce the time-lag between discoveries and their application. 1. See
Lancet,. July 18, 1953, pp. 123, 133.
AT an inquest last week the death of a child aged ten months was attributed to bronchopneumonia due to pink disease, itself the result of mercury poisoning
following "innocent overdosage" of teething-powder.’1 Last year the Minister of Health, replying to a question in the House of Commons, said that " the indiscriminate use of teething-powders containing mercury is clearly This advice has been unheeded and undesirable."2 teething-powders containing calomel are still being sold to the public without adequate warning about their
dangers.
In his article3 last week Dr. Farquhar described two cases where mercury caused or contributed to death : one child died from severe renal damage, apparently a similar condition to that reported by Wilson et al.4 ; and the second showed many of the clinical features of pink disease. The nephrotoxic action of is and these reports alone are mercury undisputed sufficient to proscribe the use of mercurials in infancy. But the role of mercury in pink disease is not yet clearly defined : that the disease is a form of poisoning by or hypersensitivity to mercury has been strongly suggested6 by the work of Fanconi5 in Switzerland and Warkany in the U.S.A. They have shown that in many cases of pink disease there is either a history of mercury ingestion or inunction or an excretion of excessive amounts of mercury in the urine. This is true also of reports from this country,7 8 Australia,9 and South Africa.lO These have demonstrated the interesting correlation between more
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Times, Dec. 3, 1953. See Lancet, 1952, i, 827. Farquhar, H. G. Ibid, Dec. 5, 1953, p. 1186. Wilson. V. K., Thomson, M. L., Holzel, A. Brit. med. J. 1952 i, 358. Fanconi, G., Botsztejn, A. Helv. pœdiat. acta, 1948, 3, 264. Warkany, J., Hubbard, D. M. J. Pediat. 1953, 42, 365. Holzel, A., James, T. Lancet, 1952, i, 441. James, G. A. Gt Ormond St J. 1951, i, 48. Clements, F. W. Med. J. Aust. 1953, ii, 213. Epstein, B. S. Afr. med. J. 1953, 27, 823.
similar
cases
observed the same type of enteritis in patients given combined course of penicillin and dihydrostreptomycin by intramuscular injection. Obviously there is need for discretion in the choice of antibiotic, to prevent postoperative infection or to treat an established infection, where the patient’s general condition is much reduced either by severe or long-continued infection or by such states as malnutrition and chronic alcoholism. For example, weighing risk against likely gain, the powerful bactericidal effect of streptomycin and penicillin is essential for the successful treatment of endocarditis caused by Streptococcus fcccalis ;; since the infection is not otherwise curable the hazard of this particularly powerful combination is justified. But it is doubtful whether such a combination can justifiably be given to prevent postoperative infection. The " broad-spectrum antibiotics-aureomycin, oxytetracycline, and chloramphenicol-have obvious attractions as prophylactics in that they are given by mouth and protect against so many organisms, particularly those of the intestinal tract. But these drugs rather often provoke some gastro-intestinal disturbance, and it is a mistake to suppose that the symptoms are always either mild or transient. At the recent Washington symposium on antibiotics5 the discovery of a new antibiotic, tetracycline (’ Achromycin ’), was announced. The chief advantage claimed for it is that it causes much less nausea, vomiting, and diarrhoea than either of
a
"
its
near
relatives, aureomycin (chlortetracycline)
oxytetracycline,
with which it shares many
or
properties.
If this is confirmed the new drug will indeed be welcome. Meanwhile in choosing prophylactics it should not be forgotten that succinylsulphathiazole by mouth and penicillin by injection provide good cover with little risk, and that moderate dosage over a short period is likely to be effective. Altogether it seems that much current practice is based on unduly pessimistic estimates of the risk of sepsis complicating operations, with the result that patients are being needlessly exposed to real dangers by over-insurance against complications which are improbable and which can readily be controlled by prompt treatment with antibiotics. There can be no substitutes for a sound aseptic technique and for watchful care during convalescence ; these will contribute far more to the safety and welfare of patients than a carefree enthusiBefore asm for hearty doses of the latest antibiotic. the era of sulphonamides and antibiotics sepsis had become a relatively rare complication of deliberate
operations. We normally
terms with our almost ungracious and certainly naive to disturb their balance suddenly in preparing for a surgical operation. We cannot by giving known antibiotics eliminate all forms of living micro-organism from the intestinal tract, and we must
intestinal
-live
on
bacteria, and it
peaceful
seems
1. Minn. Med. 1953, 36, 63. 2. Fairlie, C. W., Kendall, R. E. J. Amer. med. Ass. 3. Terplan, K. Amer. J. Path. 1953, 29, 595. 4. Janbon, L., Bertrand, J., Roux, J., Salvaing, J. Méd., Paris, 1952, 136, 59. 5. See Brit. Med. J. Nov. 7, 1953, p. 1043.
1953, 153, 90. Bull. Acad.
that suppression of the species sensitive -to the chosen antibiotic will favour proliferation of those which are insensitive. We still know little of the complicated influences governing the ecology of the bacterial population of the intestine, but common sense suggests that it may be best for the patient to weather a surgical crisis in company with the organisms with which he has come to terms. Perhaps staphylococci are not the sole cause of the enterocolitis reported by Dr. GARDNER and others, but many coagulase-positive staphylococci produce enterotoxin and may give rise to sharp outbreaks of food-poisoning.
expect
Owing to our own activities, staphylococci in hospitals are now largely resistant to the antibiotics in general use, and it has-been suggested that erythromycin, as it becomes available here, might be reserved for cases of staphylococcal enteritis. Such restraint, however, would not be in keeping with the general popularity of new antibiotics, and in any event erythromycinresistant staphylococci appear very readily. In the Washington symposium,5 LEPPER referred to a hospital in which after five months’ use of erythromycin the carrier-rate of highly resistant strains reached 75%. The remedy seems to involve, firstly, educating ourselves to use antibiotics sparingly, taking full advantage of other means of preventing surgical sepsis, and, secondly, undertaking careful and critical studies of the normal intestinal bacteria and of the influences, including antibiotics, which determine important changes in this richly varied population.
Peripheral Neuropathies FEW nosological problems can be more difficult than that of the peripheral neuropathies. Rational classification is difficult because of the wide clinical variations and the complex pathological and biochemical findings.6 Accordingly in treatment the to has been tendency apply any remedy for which success has been claimed, regardless of the type of neural disorder. Clinically the disturbance may be peripheral, in the nerve-roots, in the spinal cord, in the brain, or in the cranial nerves, but this variation only suggests varying susceptibility of the neuronal groups. Pathologically, too, the findings vary enormously. For instance, in the Guillain-Barre syndrome (infective neuronitis, infec-
polyneuritis, polyradiculoneuritis), SCHEINKER7 impressed by the pronounced swelling of nervefibres in the spinal roots and cord tracts and in the cranial and peripheral nerves ; while LOWENBERG and FOSTERdescribed degeneration of the myelin in the peripheral nerves, spinal cord, ganglia, and tive was
brain-stem. FORSTER et al.,9 on the other hand, found that the central nervous system was not materially affected. Such different pathological findings clearly reflect the differences in the clinical picture ; they are no doubt due partly to differences in the temporal evolution of the disorder. Biochemically a few features are now clearly defined. JOINER et aI.l0 showed that neuropathy due to 6. See Elkington, J. H. C., Thompson, R. H. S., Matthews, W. B. Proc. R. Soc. Med. 1952, 45, 661. 7. Scheinker, I. M. J. Neuropath. 1949, 8, 184. 8. Lowenberg, K., Foster, D. B. Arch. Neural. Psychiat., Chicago, 1945, 53, 185. 9. Forster, F. M., Brown, M., Merritt, H. H. New Engl. J. Med.
1941, 225, 51.
10. Joiner, C. 73, 431.
L., MeArdle, B., Thompson,
R. H. S.
Brain, 1950,
1247
vitamin-:B1 deficiency is associated with inhibition of system. Other workers have suggested an allergic the pyruvate-oxidase enzyme system ; and THOMPSON6 basis, emphasising the histological picture of oedema of the neural tissues leading to secondary myelin out that has pointed abnormally high blood-pyruvate with neuroin found not be levels may degeneration. These days such a hypothesis leads only patients but also with associated vitamin-13l deficiency inevitably to a trial of cortisone or corticotrophin pathy to due toxic with those in lewisite, (A.C.T.H.). Among others, BLOOD et al.12 and NEwEY neuropathies are believed These substances and LUBIN13 have reported dramatic improvement in metals. other or arsenic, the Guillain-Barré syndrome after administration of to disturb the pyruvate-oxidase system by their attrac25 mg. of corticotrophin intravenously over a period tion for the sulphhydryl groups of the enzyme In the of 8 hours each day for 5-10 days. Discontinuation deficiency neuropathies (possibly proteins. it is some diabetic reasonable to of treatment was followed by relapse, but this was forms) including administer vitamin Bi, and in the toxic neuropathies successfully countered by a further course. In this dimercaprol (BAL),which is believed to restore enzyme issue Dr. LIVERSEDGE and Dr. LEATHER report a good equilibrium. In the majority of neuropathies, however, response in a patient with polyneuritis associated there ’is no clear indication that either vitamin-B1 with periarteritis nodosa. This association is well or intoxication is at work-and this seems it seems and deficiency recognised, possible that both disorders to apply also to the rare neurological affections be due to tissue may hypersensitivity which may be associated with porphyria and with carcinoma. or due to affection of the vasa neuronal primarily nervorum. Apparently allergy may play an important The most common form is the Guilliain-Barre syndrome, and it is chiefly in this group that the part in the Guillain-Barré syndrome ; the sensitising various remedies have been assessed. VAN HAGEN agent is still unknown, but this syndrome almost 11 BAKER have described their in and invariably follows some minor infection. Furthermore experiences the polyneuritis associated with measles, mumps, 23 cases treated with a combination of vitamin B1 and dimercaprol. They found that about half of diphtheria, and even porphyria might also be explained Though the evidence is still these patients seemed to " show improvement," and by this hypothesis. the concluded that this improvement indicated that the day imperfect, may be approaching when neurocan be treated more rationally. was itself due to disturbance of the pathies syndrome enzyme 11. Van Hagen, K.
12. Blood, A., Locke, W., Carabasi, R. Ibid, 1953, 152, 139. 13. Newey, J. A., Lubin, R. I. Ibid, p. 137.
O., Baker, R. N. J. Amer. med. Ass. 1953.
151, 1465.
TEETHING-POWDERS
Annotations CLINICAL RESEARCH BOARD THE Medical Research Council announces this week the membership of the Clinical Research Board, set up in accordance with the white-paper on Clinical Research in Relation to the National Health Service.’ The board, appointed for three years after consultation with the Ministry of Health and the Department of Health for Scotland, has the following members : Sir GEOFFREY JEFFERSON, F.R.S., emeritus professor of neurosurgery, University of Manchester (chairman) ; Prof. DUGALD BAIRD, midwifery department, University of Aberdeen ; Sir HENRY COHEN, department of medicine, University of Liverpool; Prof. E. C. DODDS, F.R.S., Courtauld Institute of Biochemistry, Middlesex Hospital, London ; Sir JAMEs LEARMONTH, department of surgery, University of Edinburgh ; Prof. A. J. LEWIS, Institute of Psychiatry, Maudsley Hospital, London ; Prof. G. W. PICKERING, medical unit, St. Mary’s Hospital, London ; Prof. R. PLATT, department of medicine, University of Manchester ; Sir JAMES PATERSON Ross, surgical unit, St. Bartholomew’s Hospital, London; Sir JAMES SPENCE, department of child health, King’s College, Newcastle upon Tyne ; and Prof. B. W. WINDEYER, Meyerstein Institute of Radiotherapy, Middlesex Hospital, London. The chief medical officers of the Ministry of Health, the Department of Health for Scotland, and the Ministry of Health and Local Government in Northern Ireland will be assessors to the board, and the secretary of the Medical Research Council will attend all meetings. Dr. F. J. C. Herrald, a senior medical officer on the council’s headquarters staff, will act as secretary.
The board will be concerned with promoting whatever clinical research needs to be organised on a national basis. It will aim to ensure that all fields of inquiry are adequately covered, and will collect, collate, and distribute information in order to reduce the time-lag between discoveries and their application. 1. See
Lancet,. July 18, 1953, pp. 123, 133.
AT an inquest last week the death of a child aged ten months was attributed to bronchopneumonia due to pink disease, itself the result of mercury poisoning
following "innocent overdosage" of teething-powder.’1 Last year the Minister of Health, replying to a question in the House of Commons, said that " the indiscriminate use of teething-powders containing mercury is clearly This advice has been unheeded and undesirable."2 teething-powders containing calomel are still being sold to the public without adequate warning about their
dangers.
In his article3 last week Dr. Farquhar described two cases where mercury caused or contributed to death : one child died from severe renal damage, apparently a similar condition to that reported by Wilson et al.4 ; and the second showed many of the clinical features of pink disease. The nephrotoxic action of is and these reports alone are mercury undisputed sufficient to proscribe the use of mercurials in infancy. But the role of mercury in pink disease is not yet clearly defined : that the disease is a form of poisoning by or hypersensitivity to mercury has been strongly suggested6 by the work of Fanconi5 in Switzerland and Warkany in the U.S.A. They have shown that in many cases of pink disease there is either a history of mercury ingestion or inunction or an excretion of excessive amounts of mercury in the urine. This is true also of reports from this country,7 8 Australia,9 and South Africa.lO These have demonstrated the interesting correlation between more
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Times, Dec. 3, 1953. See Lancet, 1952, i, 827. Farquhar, H. G. Ibid, Dec. 5, 1953, p. 1186. Wilson. V. K., Thomson, M. L., Holzel, A. Brit. med. J. 1952 i, 358. Fanconi, G., Botsztejn, A. Helv. pœdiat. acta, 1948, 3, 264. Warkany, J., Hubbard, D. M. J. Pediat. 1953, 42, 365. Holzel, A., James, T. Lancet, 1952, i, 441. James, G. A. Gt Ormond St J. 1951, i, 48. Clements, F. W. Med. J. Aust. 1953, ii, 213. Epstein, B. S. Afr. med. J. 1953, 27, 823.