986 in bulk. We must not confuse the effects of insufficiency with those of lectin. crease
Department of Bacteriology and Virology, University of Manchester,
pancreatic
DAVID L. J. FREED C. HILARY BUCKLEY
Manchester M13 9PT.
DRUGS FOR PARKINSON’S DISEASE
SIR,-We disagree with your editorial on the choice of drugs parkinsonism (April 8, p. 754). You stated that "One
for
approach is to reserve the most powerful drugs for the more patients irrespective of age; another is to start young on people levodopa and older people on anticholinergics or amantadine, since levodopa is better tolerated by the young". We agree that levodopa is better tolerated by the young but this is even more true of anticholinergics. Every physician with experience of the elderly is aware of the high incidence of serious side-effects of anticholinergics in elderly patients, of which the commonest is confusion, especially in those with dementia.’1 disabled
Confusion is
not
mentioned in your editorial
as a
ENKEPHALIN IN PERIPHERAL NEUROENDOCRINE TUMOURS
SiR,-The discovery of the opiate receptor in 1973’,’
was
rapidly by the demonstration of endogenous peptides with opioid activity, the endorphins. The first, a pair of pentapeptides called leucine and methionine enkephalin, were extracted from brain in 19753 and have since been found in the nerves and endocrine cells of the gut.4 Other larger endorphin peptides, 16-31 aminoacids in length, have been extracted from the pituitarys 6 where they are found in the corticotrophs.7 Thus enkephalin and the larger endorphins appear to be intimately associated with the neuroendocrine system, so we have looked for them in tumours of that system. followed
CLINICAL FINDINGS AND LABORATORY RESULTS
symptom of
overdosage. that elderly patients with disshould be given a trial of levodopa the first line of attack. Earlier experience2,3 with this drug in the elderly gave it an undeservedly bad reputation because the dosage used was usually excessive. By starting with a very low dose and increasing cautiously, a high proportion of elderly patients will derive significant benefit.4 We advocate starting with 50 mg levodopa combined with decarboxylase inhibitor once or twice daily, and increasing by a similar amount every four or five days until a satisfactory clinical response has been achieved or side-effects appear. We hope to dissuade others from accepting your advice to use anticholinergics as the first line of treatment in the elderly, and to encourage the rational use of levodopa. We make
ability due therapy as
a
very strong
plea
parkinsonism
to
Department of Geriatric Medicine, University of Glasgow, Southern General Hospital, Glasgow G51 4TF Department of Geriatric Medicine, University of Edinburgh
F. I. CAIRD
J. WILLIAMSON
VACCINIA AND ICHTHYOSIS confirm the report by Dr Verbov and Professor McCarthy (April 22, p. 870) that ichthyosis increases susceptibility to vaccinia infection by citing my paper on Kaposi’s varicelliform eruption:S
SiR,—I
can
"Case 4 occurred during the Glasgow smallpox outbreak of 1950 and clinically resembled this disease so closely as to be admitted on April 21, 1950, to the smallpox hospital isolation compound. Four days after the onset of fever, chills, headache and.backache, at which time the patient noticed a ’blister’ on her cut hand, her face and hands swelled and ’angry spots’ appeared on these areas. Two days later these lesions were pustular, deeply set, with surrounding induration and were present on face, neck and upper limbs".
Vaccinia virus was isolated from the lesions of’this 43-yearold woman. The infection was acquired from her children who were involved in the mass vaccination. She had chronic ich-
thyosis. University Department of NORMAN R. GRIST
Broe, G. A., Caird, F. I. Med. J. Aust. 1973, i, 630. Jenkins, R. B., Groh, R. H. Lancet, 1970, ii, 177. Sacks, O. W., Messeloff, C., Schartz, W., Goldfarb, A., Kohl, M. ibid. i,
1231. F. I. in Geriatric Medicine (edited Judge); p. 171. London, 1974. 5. Grist, N. R. Glasg. med. J. 1953, 34, 1. 4.
Caird,
*
Tumour tissue was obtained at surgery from three patients with functioning adrenal medullary tumours (see table) and two patients with gastrinomas. The tissue was boiled, homogenised and, extracted three times in distilled water. Gel-filtration chromatography of the extracts was performed on a 23x11 cm ’Sephadex G25’ column with 0.1mol/l formic-acid buffer. The column was initially washed with a 1% albumin solution and calibrated with blue dextran and synthetic methionine enkephalin. Column fractions and serial dilutions of the tissue extracts were assayed for enkephalin and endorphin by
radioimmunoassay.1 Enkephalin immunoreactivity was found only in the adrenal medullary tumours. The largest amounts were in the two tumours which also produced the peptide hormone v.i.p. (vasoactive intestinal peptide). On serial dilution of the crude tissue extracts from cases 1 and 2 the curves produced were not completely parallel with metenkephalin standards, and on further analysis by gel filtration chromatography the enkephalin immunoreactivity separated into two peaks-one in the void volume and the other at a position identical to that of synthetic metenkephalin (figure). The quantity of enkephalin in the third case was insufficient for chromatography. Neither crude tissue extracts nor either chromatographic peak could be detected by an assay measuring gamma, alpha, or beta endorphin. We have clearly shown the presence of enkephalin-like immunoreactivity in tumours of peripheral neuroendocrine origin. The nature of the additional enkephalin immunoreactivity
which eluted in the void volume of the G25 column is unknown but explains the non-parallel serial dilution curves of crude tumour extract. It may represent a larger enkephalin Simon, E. J., Hiller, J. M., Edelman, I. Proc. natn. Acad Sci. U.S.A. 1973, 70, 1947. 2. Kuhar, M. J., Pert, C. B., Snyder, S. Nature, 1973, 245, 447. 3. Hughes, J., Smith, T. W., Kosterlitz, H. W., Fothergill, L. A., Morgan, B. A., Morris, H. R. ibid. 1975, 258, 577. 4. Polak, J. M., Sullivan, S. N., Bloom, S. R., Facer, P., Pearse, A. G. E. Lancet, 1977, i, 972. 5. Ling, N., Burgus, R., Guillemin, R. Proc. natn . Acad. Sci. U.S.A. 1976, 73, 1.
Infectious Diseases, Ruchill Hospital, Glasgow G20 9NB 1. 2. 3.
A.=adrenaline ; N.A.=noradrenaline; D.=dopamine; v.i.p.=vasoactive intestinal polypeptide. Detected in tissue extract only.
3942
by
W. F. Anderson and T. G.
6. 7.
Li, C. H., Chung, D. ibid. 1976, 73, 1145. Bloom, F., Battenberg, E., Rossier, J., Ling, N., Leppaluoto, J., Vargo, T., Guillemin, A. Life Sci. 1977, 20, 43.
987 A 41-year-old seaman was airlifted to hospital with a twenty-four hour history of left-sided abdominal pain associated with rigors. His condition deteriorated in transit, and on
admission to the intensive-care unit he was comatose and in a of circulatory collapse. He had previously been well apart from a right-sided pylolithotomy in 1975. The initial clinical impression of gram-negative septicaemia complicating leftsided pylonephritis was confirmed when Escherichia coli was isolated from urine cultures and Proteus spp. from blood cultures. Treatment was started with intravenous gentamicin and ampicillin. Ten days after admission when the clinical state was improving, the patient vomited altered blood and haemoglobin fell from 12.5g/dl to 9-55 g/dl over four days. The patient was given three units of blood and intravenous cimetidine (200 mg every six hours). Although no gastrointestinal bleeding was observed, the haemoglobin fell from 11.5g/dl to 7.3g/dl over the next ten days, accompanied by a lowering of the white blood-cell count (13xl0"/l to 3 x 109/1) and the platelet count (130xl0"/l to 30 x 109/1). In the absence of any other obvious cause cimetidine was withdrawn, and recovery followed. The platelet level rose to a peak of 330x 109/1 on the tenth day and then remained normal. The white blood-cell count rose to a peak of 15 x 109/1 with 17% metamyelocytes and myelocytes on the third day, then levelled off at 7 x 109/1 with a normal differential count. The haemoglobin rose gradually over the next three weeks by 1.5 g/dl with a reticulocytosis of 15% ten days after withdrawal of cimetidine. The patient’s general condition gradually improved and he was discharged three weeks later. Although any profound illness, such as a gram-negative septicaemia, may produce some degree of marrow depression the timing in this case seems to implicate cimetidine. state
Sephadex G25 chromatography of tissue enkephalin standard. Void volume was determined by blue dextran.
extracts
and met-
Royal
Cornwall
Truro, Cornwall
species or just be non-specific protein interference. It is, however, highly unlikely to be one of the recognised larger endorphin species since immunoreactivity of alpha, gamma and beta endorphin could not be detected in the tumour extracts or in any of the column fractions. Tumours of the peripheral neuroendocrine system produce many hormones, particularly catecholamines and v.i.p. Both of these substances are present in brain and v.i.p. is also found in the gut.8 The distribution of enkephalin is similarand it is therefore not surprising that it should also be present in tumours of the adrenal medualla. The pharmacophysiology of enkephalin in man is unknown and our assay is not sensitive enough to detect plasma levels. However, in future patients with phaeochromocytomas or ganglioneuromas, a full evaluation of pain threshold, gut motility, and psychiatric state before and after surgery would be nftyfat trtt
Department of Bacteriology and Virology, University of Manchester,
pancreatic
DAVID L. J. FREED C. HILARY BUCKLEY
Manchester M13 9PT.
DRUGS FOR PARKINSON’S DISEASE
SIR,-We disagree with your editorial on the choice of drugs parkinsonism (April 8, p. 754). You stated that "One
for
approach is to reserve the most powerful drugs for the more patients irrespective of age; another is to start young on people levodopa and older people on anticholinergics or amantadine, since levodopa is better tolerated by the young". We agree that levodopa is better tolerated by the young but this is even more true of anticholinergics. Every physician with experience of the elderly is aware of the high incidence of serious side-effects of anticholinergics in elderly patients, of which the commonest is confusion, especially in those with dementia.’1 disabled
Confusion is
not
mentioned in your editorial
as a
ENKEPHALIN IN PERIPHERAL NEUROENDOCRINE TUMOURS
SiR,-The discovery of the opiate receptor in 1973’,’
was
rapidly by the demonstration of endogenous peptides with opioid activity, the endorphins. The first, a pair of pentapeptides called leucine and methionine enkephalin, were extracted from brain in 19753 and have since been found in the nerves and endocrine cells of the gut.4 Other larger endorphin peptides, 16-31 aminoacids in length, have been extracted from the pituitarys 6 where they are found in the corticotrophs.7 Thus enkephalin and the larger endorphins appear to be intimately associated with the neuroendocrine system, so we have looked for them in tumours of that system. followed
CLINICAL FINDINGS AND LABORATORY RESULTS
symptom of
overdosage. that elderly patients with disshould be given a trial of levodopa the first line of attack. Earlier experience2,3 with this drug in the elderly gave it an undeservedly bad reputation because the dosage used was usually excessive. By starting with a very low dose and increasing cautiously, a high proportion of elderly patients will derive significant benefit.4 We advocate starting with 50 mg levodopa combined with decarboxylase inhibitor once or twice daily, and increasing by a similar amount every four or five days until a satisfactory clinical response has been achieved or side-effects appear. We hope to dissuade others from accepting your advice to use anticholinergics as the first line of treatment in the elderly, and to encourage the rational use of levodopa. We make
ability due therapy as
a
very strong
plea
parkinsonism
to
Department of Geriatric Medicine, University of Glasgow, Southern General Hospital, Glasgow G51 4TF Department of Geriatric Medicine, University of Edinburgh
F. I. CAIRD
J. WILLIAMSON
VACCINIA AND ICHTHYOSIS confirm the report by Dr Verbov and Professor McCarthy (April 22, p. 870) that ichthyosis increases susceptibility to vaccinia infection by citing my paper on Kaposi’s varicelliform eruption:S
SiR,—I
can
"Case 4 occurred during the Glasgow smallpox outbreak of 1950 and clinically resembled this disease so closely as to be admitted on April 21, 1950, to the smallpox hospital isolation compound. Four days after the onset of fever, chills, headache and.backache, at which time the patient noticed a ’blister’ on her cut hand, her face and hands swelled and ’angry spots’ appeared on these areas. Two days later these lesions were pustular, deeply set, with surrounding induration and were present on face, neck and upper limbs".
Vaccinia virus was isolated from the lesions of’this 43-yearold woman. The infection was acquired from her children who were involved in the mass vaccination. She had chronic ich-
thyosis. University Department of NORMAN R. GRIST
Broe, G. A., Caird, F. I. Med. J. Aust. 1973, i, 630. Jenkins, R. B., Groh, R. H. Lancet, 1970, ii, 177. Sacks, O. W., Messeloff, C., Schartz, W., Goldfarb, A., Kohl, M. ibid. i,
1231. F. I. in Geriatric Medicine (edited Judge); p. 171. London, 1974. 5. Grist, N. R. Glasg. med. J. 1953, 34, 1. 4.
Caird,
*
Tumour tissue was obtained at surgery from three patients with functioning adrenal medullary tumours (see table) and two patients with gastrinomas. The tissue was boiled, homogenised and, extracted three times in distilled water. Gel-filtration chromatography of the extracts was performed on a 23x11 cm ’Sephadex G25’ column with 0.1mol/l formic-acid buffer. The column was initially washed with a 1% albumin solution and calibrated with blue dextran and synthetic methionine enkephalin. Column fractions and serial dilutions of the tissue extracts were assayed for enkephalin and endorphin by
radioimmunoassay.1 Enkephalin immunoreactivity was found only in the adrenal medullary tumours. The largest amounts were in the two tumours which also produced the peptide hormone v.i.p. (vasoactive intestinal peptide). On serial dilution of the crude tissue extracts from cases 1 and 2 the curves produced were not completely parallel with metenkephalin standards, and on further analysis by gel filtration chromatography the enkephalin immunoreactivity separated into two peaks-one in the void volume and the other at a position identical to that of synthetic metenkephalin (figure). The quantity of enkephalin in the third case was insufficient for chromatography. Neither crude tissue extracts nor either chromatographic peak could be detected by an assay measuring gamma, alpha, or beta endorphin. We have clearly shown the presence of enkephalin-like immunoreactivity in tumours of peripheral neuroendocrine origin. The nature of the additional enkephalin immunoreactivity
which eluted in the void volume of the G25 column is unknown but explains the non-parallel serial dilution curves of crude tumour extract. It may represent a larger enkephalin Simon, E. J., Hiller, J. M., Edelman, I. Proc. natn. Acad Sci. U.S.A. 1973, 70, 1947. 2. Kuhar, M. J., Pert, C. B., Snyder, S. Nature, 1973, 245, 447. 3. Hughes, J., Smith, T. W., Kosterlitz, H. W., Fothergill, L. A., Morgan, B. A., Morris, H. R. ibid. 1975, 258, 577. 4. Polak, J. M., Sullivan, S. N., Bloom, S. R., Facer, P., Pearse, A. G. E. Lancet, 1977, i, 972. 5. Ling, N., Burgus, R., Guillemin, R. Proc. natn . Acad. Sci. U.S.A. 1976, 73, 1.
Infectious Diseases, Ruchill Hospital, Glasgow G20 9NB 1. 2. 3.
A.=adrenaline ; N.A.=noradrenaline; D.=dopamine; v.i.p.=vasoactive intestinal polypeptide. Detected in tissue extract only.
3942
by
W. F. Anderson and T. G.
6. 7.
Li, C. H., Chung, D. ibid. 1976, 73, 1145. Bloom, F., Battenberg, E., Rossier, J., Ling, N., Leppaluoto, J., Vargo, T., Guillemin, A. Life Sci. 1977, 20, 43.
987 A 41-year-old seaman was airlifted to hospital with a twenty-four hour history of left-sided abdominal pain associated with rigors. His condition deteriorated in transit, and on
admission to the intensive-care unit he was comatose and in a of circulatory collapse. He had previously been well apart from a right-sided pylolithotomy in 1975. The initial clinical impression of gram-negative septicaemia complicating leftsided pylonephritis was confirmed when Escherichia coli was isolated from urine cultures and Proteus spp. from blood cultures. Treatment was started with intravenous gentamicin and ampicillin. Ten days after admission when the clinical state was improving, the patient vomited altered blood and haemoglobin fell from 12.5g/dl to 9-55 g/dl over four days. The patient was given three units of blood and intravenous cimetidine (200 mg every six hours). Although no gastrointestinal bleeding was observed, the haemoglobin fell from 11.5g/dl to 7.3g/dl over the next ten days, accompanied by a lowering of the white blood-cell count (13xl0"/l to 3 x 109/1) and the platelet count (130xl0"/l to 30 x 109/1). In the absence of any other obvious cause cimetidine was withdrawn, and recovery followed. The platelet level rose to a peak of 330x 109/1 on the tenth day and then remained normal. The white blood-cell count rose to a peak of 15 x 109/1 with 17% metamyelocytes and myelocytes on the third day, then levelled off at 7 x 109/1 with a normal differential count. The haemoglobin rose gradually over the next three weeks by 1.5 g/dl with a reticulocytosis of 15% ten days after withdrawal of cimetidine. The patient’s general condition gradually improved and he was discharged three weeks later. Although any profound illness, such as a gram-negative septicaemia, may produce some degree of marrow depression the timing in this case seems to implicate cimetidine. state
Sephadex G25 chromatography of tissue enkephalin standard. Void volume was determined by blue dextran.
extracts
and met-
Royal
Cornwall
Truro, Cornwall
species or just be non-specific protein interference. It is, however, highly unlikely to be one of the recognised larger endorphin species since immunoreactivity of alpha, gamma and beta endorphin could not be detected in the tumour extracts or in any of the column fractions. Tumours of the peripheral neuroendocrine system produce many hormones, particularly catecholamines and v.i.p. Both of these substances are present in brain and v.i.p. is also found in the gut.8 The distribution of enkephalin is similarand it is therefore not surprising that it should also be present in tumours of the adrenal medualla. The pharmacophysiology of enkephalin in man is unknown and our assay is not sensitive enough to detect plasma levels. However, in future patients with phaeochromocytomas or ganglioneuromas, a full evaluation of pain threshold, gut motility, and psychiatric state before and after surgery would be nftyfat trtt
