1149
posterior aspects of the hypothenar emminence, therefore from all the ulnar innervated muscles therein.’ We concede, however, that this point is not clear in our paper and may have misled you. Commenting on our electrophysiological assessment of sensory function you state that "most electrophysiological laboratories require three and a half digits for median-nerve function, one and a half digits for ulnar-nerve function and an assessment of the radial nerve for control purposes", an opinion supported by reference to unpublished data. We disagree. We found2no significant differences in the percentage reductions in sensory-nerve action-potential amplitudes or sensory conduction velocities between the thumb, index, and middle fingers in patients with median-nerve section and repair. For the type of information we were seeking, there was no advantage in studying three and a half fingers rather than one. Your reason for suggesting the use of the radial nerve for control purposes is obscure. We used the normal nerves of the intact hand for control studies. While we agree that needle electromyography is an important investigative tool in these patients, we entirely disagree that this technique "can indicate the number of motor units engendered by voluntary effort or electrical stimulation". The assessment of the number of functioning motor units during voluntary activity by needle electromyography is at best a gross approximation, and with electrical stimulation it is useless.3 Even in normal muscle, because of the very small pick-up area of the concentric needle electrode (0.5 mm radius from needle tip), no more than about 25 motor units can be detected from any one point.4,5 In the disturbed architecture of the reinnervating muscle it is unlikely that even that number could be identified. The concentric needle electrode cannot be used to count functioning motor units in normal or abnormal muscle. You imply that we did not undertake needle electromyography. Concentric needle electrode studies were done on half of our patients to measure the amplitudes of the voluntarily evoked motor unit potentials, an index of the state of reinnervation in individual units, and to record the presence of fibrillation. This is the only useful information that technique can provide in these circumstances. The statement that "measurement of conduction velocity reflects only the number of regenerating fibres" does not seem relevant to our paper,’ even so it is incorrect. Most, if not all, of the motor fibres proximal to the site of section are regenerating. The motor-conduction velocity values in nerve regeneration, especially in the early stages, are determined by the diameters of those motor axons that have successfully traversed the site of section and made functional contact with the target muscle. These points are fully dealt with in our paper.1 On the question of anomalous innervation, we have indicated that this may be detected by the occurrence of unexpectedly early signs of reinnervation on needle electromyography. We are not sure what you mean by "if anomalous innervation is to be identified, serial observations from an early baseline are essential". We do agree with your editorial that this is a very difficult subject to study, with many variables, including age, technique, surgical skill, type of lesion, and method of repair. We were aware of these limitations when we embarked on our investigation. We did consider the alternative study you suggested but the different categories of patient with regard to age, type of repair, surgeon, follow-up, and so on would mean that sufficient data would be unlikely to accumulate even over ten years. We preferred a more realistic, if modest, approach. None of the opinions expressed on various aspects of our study* is supported by reference to published work: twice your
recording
AChE activity in amniotic fluid from non-N.T.D. pregnancies. Blood contaminated samples are indicated by open circles.
maternal erythrocytes were found; the raised AChE activity is not caused by erythrocyte or other membranes since all samples were centrifuged before assay; there is no correlation between butyrylcholinesterase, AChE, and ot-fetoprotein concentrations in the contaminated fluids so none of these, alone or in combination, unequivocally indicate anything but gross blood contamination. Department of Human Physiology, Centre for Neuroscience, Flinders University of South Australia, Bedford Park, South Australia 5042; and Department of Clinical Pathology, Adelaide Children’s Hospital
I. W. CHUBB P. M. PILOWSKY A. J. HODGSON A. C. POLLARD
PERIPHERAL-NERVE REPAIR flattered that you should devote half 14 to a critique of our paper on perieditorial April pheral-nerve injuries,’ we would like to correct several misrepresentations and basic electrophysiological misconceptions contained therein. Some of your comments seem imprecise but we will deal with them as we understand the meaning. You suggest that "The abductor digiti minimi is not sufficient on its own to reflect the behaviour of the ulnar nerve and the first dorsal interosseus and flexor carpi ulnaris should be included". In 75% of our patients the ulnar-nerve lesion was at the wrist. In only two of the remaining patients was the nerve supply to flexor carpi ulnaris affected. Study of that muscle would have been pointless. The first dorsal interosseus muscle is especially unsuitable in this type of study because of the difficulty of placing surface electrodes over its motor point and because of its proximity to the median innervated abductor pollicis brevis. We did not, however, record from the abductor digiti minimi alone. The surface electrodes (5 mm by 6 cm silver foil strips)-encompassed the anterior, lateral, and
SIR,-While
we are
of
your
1. Donoso, R.
2. 3. 4.
Ballantyne, J. P., Campbell, M. J. ibid. 1973, 36, 797. Ballantyne, J. P., Hansen, S. ibid 1975, 38, 417 Buchthal, F., Rosenfalck, P., Erminio, F. Neurology, Minneapolis, 1960, 10,
5.
Buchthal, F., Guld, C., Rosenfalck, P. Acta physiol. scand. 1957, 39, 83.
S., Ballantyne, J. P., Hansen, S. J. Neurol. Neurosurg. Psychiat.
1979, 42, 97.
398.
1150
unsigned
editorial alludes
to
the
same
unpublished
source.
If
The Lancet is to maintain its reputation for fairness it should review its editorial policy on this practice. Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, and Department of Clinical Physics and Bio-Engineering, Glasgow
JOHN P. BALLANTYNE STIG HANSEN
THE NEW CONSULTANT CONTRACT
SIR,-It is interesting to see, in your review of Prof. James McCormick’s book The Doctor: Father Figure or Plumber (May 12, p. 1008), unprofessional conduct described as working to the clock, demanding overtime, and striking. This, it is stated, is likely to be seen in doctors whose incomes are continuing to fall in relative terms. Two of these features-working to the clock and demanding overtime-are to be seen in the proposed new so-called "work-sensitive" consultant contract. North Middlesex Hospital, London N18 1QX
M. G. REVILL
CLINICAL MEDICAL OFFICERS
SIR,-I write to support the view of Professor Forfar and the presidents of the Royal Colleges of Physicians and the British Pxdiatric Association in their letter of May 12, that the natural affiliation of most clinical medical officers "lies not with community medicine but with clinical paediatrics." This has been the expressed view of my Faculty from our beginning. We emphasise our abiding concern for the future of the child health service and acknowledge warmly our historical responsibility towards our clinical medical officer colleagues, who must have the same entitlement to vocational training and professional advancement in their chosen area of work as have those in other branches of medicine. Specialists in community medicine will, of course, continue to have an important role in the child health services in determining need for and facilitating the work of these services in the community. Faculty of Community Medicine of the Royal Colleges of Physicians of the United Kingdom, Royal College of Physicians, London NW1 4LE
JOHN BROTHERSTON, President
EDITORIAL INDEPENDENCE OF PRESCRIBERS’
JOURNAL SIR,-While applaud the publication of Prescribers’ journal and its circulation free of charge to all prescribing docwe
in the U.K., we feel we should draw attention to an incident which seems to indicate a form of censorship on the journal’s contents which may be unacceptable. One of us (J. H.) was invited to write a piece for Prescribers’ journal on the treatment of cardiac failure. In keeping with modern concepts and practice of treatment for this condition, the use of vasodilators such as nitrates was included in the discussion. To our surprise the manuscript was returned with a request that this section be omitted because cardiac failure has not yet been approved by the Committee on Safety of Medicines (C.S.M.) as an indication for use of drugs of this type, although they are well used for other cardiac indications such as angina and hypotension. After further correspondence, the Editorial Board of Prescribers’ Journal would not move from this
tors
which the Government-sponsored Prescribers’ Journal cannot publish guidance on the use of a medicine for a condition which has not been specifically approved by another Government body, the C.S.M. The C.S.M. itself does not initiate approval of a new indication unless requested to do so by the manufacturers of the medicine. Surely, doctors should not be deprived of advice on modern forms of drug treatment of which they may well be aware from other sources, nor should patients be deprived of their use, because of such censorship. The Editorial Board of Prescribers’ Journal should be freed from any restraints imposed by its Government sponsorship. Readers of the journal should be able to have confidence in the objectivity, impartiality, and excellence of its advice. St. Bartholomew’s Hospital Medical College, London EC1A 7BE
J. HAMER P. TURNER
NEUTROPENIA AFTER CONSECUTIVE TREATMENT COURSES WITH NAFCILLIN AND PIPERACILLIN
SIR,-Reversible neutropenia is an infrequent but wellknown complication of therapy with penicillin antibiotics and is most commonly associated with the administration of antistaphylococcal, semisynthetic penicillins. The administration of piperacillin sodium, a new semisynthetic penicillin with increased activity against gram-negative organisms, was associated with reversible leukopenia in 1 of 1266 patients who received the drug during Japanese trials (data on file of Lederle Laboratories). Dickinson et aU noted transient neutropenia in 1 of 16 patients studied in the United States. We have cared for a 46-year-old male with chronic osteomyelitis due to Staphylococcus aureus and Pseudomonas ceruginosa in whom neutropenia developed (absolute neutrophil-count 0 - 49 x 109/1) in association with relative eosinophilia (11%) on the 28th day of therapy with nafcillin and tobramycin. A bone-marrow biopsy done at that time showed a maturation arrest of the myeloid series. 4 days after nafcillin had been discontinued and while he was still receiving tobramycin, his peripheral blood contained 3.60 x 109/1 neutrophils and 0-42xl0’’/l eosinophils. Tobramycin was discontinued at this time because of ototoxicity. 10 days after nafcillin had been discontinued, treatment with piperacillin sodium, 4 g intravenously every 4 h, was started because of persistent pseudomonas osteomyelitis. At the start of therapy, the patient’s blood contained 5.50 x 109/1 neutrophils and no eosinophils. On the 17th day of therapy, his eosinophil-count (0.43x109/1) once again rose but his neutrophil-count (2.56 x 109/1) was still normal. 1 week later, his neutrophil-count was 0.07x109/1 and eosinophils had increased to 0.88x109/1. Piperacillin therapy was discontinued, and his neutrophil-count rose to 2.76x109/1 2 days later. His leucocyte-count subsequently returned to normal. All penicillin antibiotics may be associated with neutropenia. The neutropenia in our patient probably had an immune basis. This is suggested by the eosinophilia that accompanied neutropenia in association with the administration of two different penicillin antibiotics. Administration of any penicillin antibiotic to a patient who has previously had neutropenia in association with another penicillin antibiotic should be done with caution and careful hxmatological monitoring. C. WILSON G. GREENHOOD J. S. REMINGTON
Stanford
University Medical Center, Stanford, California 94305, U.S.A
K. L. VOSTI
position. It
seems
that
a
bureaucratic
impasse has been reached in
1.
Dickinson,
G.
M., Droller, D. G., Greenman, R. L., Hoffman, T. A. 18th on Antimicrobial Agents and Chemotherapy
interscience conference 1.
Lancet, 1978, i, 972.
(Atlanta, Oct. 1-4, 1978); abstr.
166.
posterior aspects of the hypothenar emminence, therefore from all the ulnar innervated muscles therein.’ We concede, however, that this point is not clear in our paper and may have misled you. Commenting on our electrophysiological assessment of sensory function you state that "most electrophysiological laboratories require three and a half digits for median-nerve function, one and a half digits for ulnar-nerve function and an assessment of the radial nerve for control purposes", an opinion supported by reference to unpublished data. We disagree. We found2no significant differences in the percentage reductions in sensory-nerve action-potential amplitudes or sensory conduction velocities between the thumb, index, and middle fingers in patients with median-nerve section and repair. For the type of information we were seeking, there was no advantage in studying three and a half fingers rather than one. Your reason for suggesting the use of the radial nerve for control purposes is obscure. We used the normal nerves of the intact hand for control studies. While we agree that needle electromyography is an important investigative tool in these patients, we entirely disagree that this technique "can indicate the number of motor units engendered by voluntary effort or electrical stimulation". The assessment of the number of functioning motor units during voluntary activity by needle electromyography is at best a gross approximation, and with electrical stimulation it is useless.3 Even in normal muscle, because of the very small pick-up area of the concentric needle electrode (0.5 mm radius from needle tip), no more than about 25 motor units can be detected from any one point.4,5 In the disturbed architecture of the reinnervating muscle it is unlikely that even that number could be identified. The concentric needle electrode cannot be used to count functioning motor units in normal or abnormal muscle. You imply that we did not undertake needle electromyography. Concentric needle electrode studies were done on half of our patients to measure the amplitudes of the voluntarily evoked motor unit potentials, an index of the state of reinnervation in individual units, and to record the presence of fibrillation. This is the only useful information that technique can provide in these circumstances. The statement that "measurement of conduction velocity reflects only the number of regenerating fibres" does not seem relevant to our paper,’ even so it is incorrect. Most, if not all, of the motor fibres proximal to the site of section are regenerating. The motor-conduction velocity values in nerve regeneration, especially in the early stages, are determined by the diameters of those motor axons that have successfully traversed the site of section and made functional contact with the target muscle. These points are fully dealt with in our paper.1 On the question of anomalous innervation, we have indicated that this may be detected by the occurrence of unexpectedly early signs of reinnervation on needle electromyography. We are not sure what you mean by "if anomalous innervation is to be identified, serial observations from an early baseline are essential". We do agree with your editorial that this is a very difficult subject to study, with many variables, including age, technique, surgical skill, type of lesion, and method of repair. We were aware of these limitations when we embarked on our investigation. We did consider the alternative study you suggested but the different categories of patient with regard to age, type of repair, surgeon, follow-up, and so on would mean that sufficient data would be unlikely to accumulate even over ten years. We preferred a more realistic, if modest, approach. None of the opinions expressed on various aspects of our study* is supported by reference to published work: twice your
recording
AChE activity in amniotic fluid from non-N.T.D. pregnancies. Blood contaminated samples are indicated by open circles.
maternal erythrocytes were found; the raised AChE activity is not caused by erythrocyte or other membranes since all samples were centrifuged before assay; there is no correlation between butyrylcholinesterase, AChE, and ot-fetoprotein concentrations in the contaminated fluids so none of these, alone or in combination, unequivocally indicate anything but gross blood contamination. Department of Human Physiology, Centre for Neuroscience, Flinders University of South Australia, Bedford Park, South Australia 5042; and Department of Clinical Pathology, Adelaide Children’s Hospital
I. W. CHUBB P. M. PILOWSKY A. J. HODGSON A. C. POLLARD
PERIPHERAL-NERVE REPAIR flattered that you should devote half 14 to a critique of our paper on perieditorial April pheral-nerve injuries,’ we would like to correct several misrepresentations and basic electrophysiological misconceptions contained therein. Some of your comments seem imprecise but we will deal with them as we understand the meaning. You suggest that "The abductor digiti minimi is not sufficient on its own to reflect the behaviour of the ulnar nerve and the first dorsal interosseus and flexor carpi ulnaris should be included". In 75% of our patients the ulnar-nerve lesion was at the wrist. In only two of the remaining patients was the nerve supply to flexor carpi ulnaris affected. Study of that muscle would have been pointless. The first dorsal interosseus muscle is especially unsuitable in this type of study because of the difficulty of placing surface electrodes over its motor point and because of its proximity to the median innervated abductor pollicis brevis. We did not, however, record from the abductor digiti minimi alone. The surface electrodes (5 mm by 6 cm silver foil strips)-encompassed the anterior, lateral, and
SIR,-While
we are
of
your
1. Donoso, R.
2. 3. 4.
Ballantyne, J. P., Campbell, M. J. ibid. 1973, 36, 797. Ballantyne, J. P., Hansen, S. ibid 1975, 38, 417 Buchthal, F., Rosenfalck, P., Erminio, F. Neurology, Minneapolis, 1960, 10,
5.
Buchthal, F., Guld, C., Rosenfalck, P. Acta physiol. scand. 1957, 39, 83.
S., Ballantyne, J. P., Hansen, S. J. Neurol. Neurosurg. Psychiat.
1979, 42, 97.
398.
1150
unsigned
editorial alludes
to
the
same
unpublished
source.
If
The Lancet is to maintain its reputation for fairness it should review its editorial policy on this practice. Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, and Department of Clinical Physics and Bio-Engineering, Glasgow
JOHN P. BALLANTYNE STIG HANSEN
THE NEW CONSULTANT CONTRACT
SIR,-It is interesting to see, in your review of Prof. James McCormick’s book The Doctor: Father Figure or Plumber (May 12, p. 1008), unprofessional conduct described as working to the clock, demanding overtime, and striking. This, it is stated, is likely to be seen in doctors whose incomes are continuing to fall in relative terms. Two of these features-working to the clock and demanding overtime-are to be seen in the proposed new so-called "work-sensitive" consultant contract. North Middlesex Hospital, London N18 1QX
M. G. REVILL
CLINICAL MEDICAL OFFICERS
SIR,-I write to support the view of Professor Forfar and the presidents of the Royal Colleges of Physicians and the British Pxdiatric Association in their letter of May 12, that the natural affiliation of most clinical medical officers "lies not with community medicine but with clinical paediatrics." This has been the expressed view of my Faculty from our beginning. We emphasise our abiding concern for the future of the child health service and acknowledge warmly our historical responsibility towards our clinical medical officer colleagues, who must have the same entitlement to vocational training and professional advancement in their chosen area of work as have those in other branches of medicine. Specialists in community medicine will, of course, continue to have an important role in the child health services in determining need for and facilitating the work of these services in the community. Faculty of Community Medicine of the Royal Colleges of Physicians of the United Kingdom, Royal College of Physicians, London NW1 4LE
JOHN BROTHERSTON, President
EDITORIAL INDEPENDENCE OF PRESCRIBERS’
JOURNAL SIR,-While applaud the publication of Prescribers’ journal and its circulation free of charge to all prescribing docwe
in the U.K., we feel we should draw attention to an incident which seems to indicate a form of censorship on the journal’s contents which may be unacceptable. One of us (J. H.) was invited to write a piece for Prescribers’ journal on the treatment of cardiac failure. In keeping with modern concepts and practice of treatment for this condition, the use of vasodilators such as nitrates was included in the discussion. To our surprise the manuscript was returned with a request that this section be omitted because cardiac failure has not yet been approved by the Committee on Safety of Medicines (C.S.M.) as an indication for use of drugs of this type, although they are well used for other cardiac indications such as angina and hypotension. After further correspondence, the Editorial Board of Prescribers’ Journal would not move from this
tors
which the Government-sponsored Prescribers’ Journal cannot publish guidance on the use of a medicine for a condition which has not been specifically approved by another Government body, the C.S.M. The C.S.M. itself does not initiate approval of a new indication unless requested to do so by the manufacturers of the medicine. Surely, doctors should not be deprived of advice on modern forms of drug treatment of which they may well be aware from other sources, nor should patients be deprived of their use, because of such censorship. The Editorial Board of Prescribers’ Journal should be freed from any restraints imposed by its Government sponsorship. Readers of the journal should be able to have confidence in the objectivity, impartiality, and excellence of its advice. St. Bartholomew’s Hospital Medical College, London EC1A 7BE
J. HAMER P. TURNER
NEUTROPENIA AFTER CONSECUTIVE TREATMENT COURSES WITH NAFCILLIN AND PIPERACILLIN
SIR,-Reversible neutropenia is an infrequent but wellknown complication of therapy with penicillin antibiotics and is most commonly associated with the administration of antistaphylococcal, semisynthetic penicillins. The administration of piperacillin sodium, a new semisynthetic penicillin with increased activity against gram-negative organisms, was associated with reversible leukopenia in 1 of 1266 patients who received the drug during Japanese trials (data on file of Lederle Laboratories). Dickinson et aU noted transient neutropenia in 1 of 16 patients studied in the United States. We have cared for a 46-year-old male with chronic osteomyelitis due to Staphylococcus aureus and Pseudomonas ceruginosa in whom neutropenia developed (absolute neutrophil-count 0 - 49 x 109/1) in association with relative eosinophilia (11%) on the 28th day of therapy with nafcillin and tobramycin. A bone-marrow biopsy done at that time showed a maturation arrest of the myeloid series. 4 days after nafcillin had been discontinued and while he was still receiving tobramycin, his peripheral blood contained 3.60 x 109/1 neutrophils and 0-42xl0’’/l eosinophils. Tobramycin was discontinued at this time because of ototoxicity. 10 days after nafcillin had been discontinued, treatment with piperacillin sodium, 4 g intravenously every 4 h, was started because of persistent pseudomonas osteomyelitis. At the start of therapy, the patient’s blood contained 5.50 x 109/1 neutrophils and no eosinophils. On the 17th day of therapy, his eosinophil-count (0.43x109/1) once again rose but his neutrophil-count (2.56 x 109/1) was still normal. 1 week later, his neutrophil-count was 0.07x109/1 and eosinophils had increased to 0.88x109/1. Piperacillin therapy was discontinued, and his neutrophil-count rose to 2.76x109/1 2 days later. His leucocyte-count subsequently returned to normal. All penicillin antibiotics may be associated with neutropenia. The neutropenia in our patient probably had an immune basis. This is suggested by the eosinophilia that accompanied neutropenia in association with the administration of two different penicillin antibiotics. Administration of any penicillin antibiotic to a patient who has previously had neutropenia in association with another penicillin antibiotic should be done with caution and careful hxmatological monitoring. C. WILSON G. GREENHOOD J. S. REMINGTON
Stanford
University Medical Center, Stanford, California 94305, U.S.A
K. L. VOSTI
position. It
seems
that
a
bureaucratic
impasse has been reached in
1.
Dickinson,
G.
M., Droller, D. G., Greenman, R. L., Hoffman, T. A. 18th on Antimicrobial Agents and Chemotherapy
interscience conference 1.
Lancet, 1978, i, 972.
(Atlanta, Oct. 1-4, 1978); abstr.
166.
