502
positive findings. We share the scepticism of Candelaresi and hope that others will confirm or refute our results. Medizinische Klinik, Stadtspital Triemli Zürich, 8063 Zürich, Switzerland
et
al.
A. L. BLUM
PURPLE URINE BAGS
SIR,-A similar incident to that described by Mr Barlow and Mr Dickson (Jan. 28, p. 220) happened in this hospital when, for a day or two, the plastic urine bag and urine from an incontinent, elderly patient were noted to be bright purple. At first we thought that the colour was due to cutaneous absorption of coal-tar ointment (given for extensive psoriasis) but then similar, albeit less striking discoloration of urine and urine bag was noted in another elderly patient not on this treatment.
On
spectral analysis
of the urine
we
found, unlike Barlow
and Dickson, a peak at 520 nm in chloroform solution with no shoulder at 600 nm. Furthermore in patients with contaminated bowel syndrome or tropical sprue indicanuria is common, but these urines (after treatment with an oxidising agent) show a peak at 600 nm when extracted in chloroform. We are therefore not convinced that in our patient the colour was due to indigo (produced by oxidation of indican). Perhaps the purple colour we observed resulted from exposure of urine to a contaminant in the plastic catheter bag rather than from exposure to air. Certainly indicanuria in patients with contaminated bowel syndrome or tropical sprue leads to a blue colour only when the urine is treated with an oxidising agent such as sodium hypochlorite powder). Similarly traces of bleaching agents may also be important in producing the blue discoloration (due to indigo) in the rare blue diaper syndrome.1
(bleaching
Departments
of Clinical
Chemistry
and Thoracic Medicine, East Birmingham Hospital, Birmingham B9 5ST
H. G. SAMMONS C. SKINNER J. FIELDS
SIR,-Purple discolouration of urine bags is well-recognised anecdotal basis in geriatric units, and in the past 2 years we have seen four such cases in Cambridge. All were women, aged 79-97 (mean 87), with indwelling urinary catheters; all were poorly ambulant or chair-fast continuing-care patients on an
with moderate to severe dementia. We have examined our most recent case and find the blue pigment’s organic solubility as described by Mr Barlow and Mr Dickson. Its spectroscopic behaviour is also similar-i.e., a peak at 550 nm and a subsidiary peak at approximately 600 nm.
The idea that constipation is the primary mechanism for excessive indoxyl-sulphate production is attractive since these elderly patients have much prolonged gut transit-times.2 However, if this is the explanation why is the colour reaction not universal in such patients rather than just an occasional curiosity ? Associated urinary alkalinity favours indigo deposition,3 and all our patients had chronic urinary-tract infections with Pseudomonas ceruginosa alone or mixed with Proteus spp. While investigating this subject we found that indigo as a cause of blue urine was well described as long ago as 1857.’* Department of Geriatric Medicine, Chesterton Hospital, Cambridge CB4 1PT
BRIAN PAYNE
Department of Clinical Biochemistry, Addenbrooke’s Hospital, Cambridge CB2 2QR
ANDREW GRANT
1. Drummond, K. N.,
Alfred, F. M., Ulstrom, R. A., Good, R. A. Am. J. Med. 1964, 37, 928. 2. Brocklehurst, J. C., Kahn, M. Y. Geront. clin. 1969, 11, 293. 3. Harrison, G. A. Chemical Methods in Clinical Medicine; p. 73. London, 1949. 4.
Golding Bird. Urinary Deposits: their Diagnosis, Pathology and Therapeutical Indications; p. 331. London, 1857.
BACTERIAL CONTAMINATION OF THE SMALL BOWEL IN THE ELDERLY
SIR The relevance, diagnosis, and treatment of bacterial contamination of the upper small bowel evokes continued interest. Roberts et al.’ suggest that bacterial colonisation of the upper small bowel may produce non-specific symptoms unrelated to the gut and may occur in the elderly in the absence of the usually associated conditions-small-bowel stasis, blind loop, or abnormal immunological mechanisms. They suggest that the 14C-glycine-glycocholic-acid (G.C.A.) breath test is adequate for diagnosis and that the symptoms are readily relieved by treatment with broad-spectrum antibiotics. We too have encountered small-bowel colonisation in the elderly in the absence of gastrointestinal disease, illustrated by the three cases described below, but have reached different conclusions. A 77-year-old man was referred for investigation with an 18-month history of diarrhoea associated with urgency and occasional incontinence and 9 kg weight-loss. There were no other symptoms. X-ray investigation and mucosal biopsy showed no structural abnormality of the gastrointestinal tract and there was no biochemical or haematological evidence of malabsorption. A G.C.A. breath test was abnormal, and Staphylococcus aureus (107/ml), non-hæmolytic streptococci (107/ml), and enterococci (107/ml) were cultured from the jejunal aspirate. Treatment with ampicillin and co-trimoxazole produced no improvement in symptoms. Repeat jejunal culture showed colonisation with the same organism plus bacteroides (106/ml), but further treatment with antibiotics produced no improvement. A high-fibre diet produced a complete remission. A 63-year-old woman presented with tiredness, diarrhoea, and some weight-loss. There was no structural abnormality of the gastrointestinal tract on X-ray or mucosal biopsy. There was a minimal steatorrhoea (22.5 mmol/day) but all other tests for malabsorption were normal. Jejunal culture yielded enterococci (105/ml), Streptococcus viridans (104/ml), corynebacterium (105/ml), and fusobacterium (106/ml). Treatment with ampicillin and metronidazole followed by cephalexin and metronidazole did not improve symptoms although after treatment the jejunal aspirate was sterile. The symptoms eventually responded satisfactorily to aluminium hydroxide and chole-
styramine. A 93-year-old man presented with diarrhoea, weight loss, lethargy, and considerable malaise. Investigation revealed no structural abnormality of the gastrointestinal tract and no evidence of malabsorption. A G.C.A. breath test was abnormal; jejunal aspiration was unsuccessful. Treatment with co-trimoxazole produced some improvement in diarrhoea and general well-being which lasted for 2 months but recurrent symptoms were not controlled by further antibiotics. These three patients support the suggestion that there may be abnormal numbers of organisms in the small bowel of elderly patients who have none. of the usual conditions associated with bacterial contamination of the small bowel. Howpatients had diarrhoea and two complained of considerable tiredness, malaise, and weight-loss, the sort of symptoms emphasised by the Newcastle workers. Two of our patients had abnormal breath tests but we do not share the confidence of Roberts et al. in this test. Our experience with over 200 tests done concurrently with jejunal aspirates have shown such a high frequency of errors-30% false positive results in the presence of anaerobic organisms and 25% false negative results-that we feel the test is unhelpful diagnostically and no longer use it. The presence of abnormal smallbowel flora is clearly related to the clinical features of the classical blind-loop syndrome and antibiotic therapy brings clinical improvement. Our experience with patients like those described here and patients with previous gastric surgery and abnormal jejunal bacteriology has been that antibiotic therapy produces disappointing clinical results even though the upper small bowel may be sterilised. Bacterial culture is required for ever, all these
1.
Roberts, S. H., James, O., Jarvis, E. H. Lancet, 1977, ii, 1193.
503 the accurate diagnosis of small-bowel contamination in these patients and jejunal aspiration and culture with an open-ended tube is usually both simple and well tolerated. However, aspiration and culture of fasting gastric juice may suffice as an alternative as we have found that the results closely mirror those of small-bowel culture when the two examinations are
carried out concurrently. It seems that there are frequently abnormal numbers of bacteria in the upper small bowel in patients with a variety of general and gastrointestinal complaints and who are either old, have gastric achlorhydria, or have had peptic-ulcer surgery. However, the relationship of these bacteria to the clinical problem is conjectural and will be clarified only by further studies with accurate ieiunal bacteriolosv.
Gastrointestinal Centre, Southern General Hospital, Glasgow G514TF
R. J. HOLDEN P. MILLS L. CRAIG J. D. SLEIGH I. MACKENZIE W. WATSON G. WATKINSON G. P. CREAN
POST-THYROIDECTOMY THYROTOXICOSIS
SIR, The study reported by Dr Kalk and his colleagues (Feb. 11, p. 291) confirms previous reports that post-thyroidectomy recurrent hyperthyroidism occurs in varying but often large numbers of patients and re-emphasises the need for longterm surveillance in chronic disease, including late-onset recurrences or thyroid failure after treatment of hyperthyroidism.2.3 The studies Kalk et al. cite are of prevalence (not incidence), and are inevitably based on retrospective examination of survivors of those treated; the risk of recurrent hyperthyroidism will only be determined by measuring its incidence in longitudinal studies in defined patient groups. Such a plan for life-long follow-up, implemented in 1968,4 is now being evaluated by, for example, life-table techniques to estimate the cumulative probability of events such as recurrence and hypothyroidism after destructive therapy for hyperthyroidism. Kalk et al. refer to our studies5 on factors determining the long-term response to subtotal thyroidectomy but do not emphasise that environmental factors, such as dietary iodine and the variation in levels of autoimmune thyroiditis in different populations, may together be more important as determinants of recurrences than is remnant size alone. Comments on the relation between remnant size and outcome of surgery in different centres are probably meaningless unless they are accompanied by estimates of both the frequency and severity of thyroiditis in the gland and of the proportion of postoperative patients in whom the underlying disease remains active.6 Such activity may be identified by T3 suppression or T.R.H. stimulation tests (although there is disagreement about the comparability of the two techniques) and probably represent the only subgroup at risk of recurrent hyperthyroidism. Large remnants will never cause a recurrence in those patients in whom the extrapituitary stimulus to the gland has remitted and similarly a small remnant may not prevent it in those in whom the stimulus persists. Over one quarter of the Johannesburg patients were Black Africans in whom the frequency of autoimmune types of thy1.
Small,
w. r.
Lancet, 1967, i, 997.
2. Crooks, J. in Computers in the Service of Medicine (edited by G. McLachlan and R. A. Shegog) Nuffield Provincial Hospitals Trust, 1968. 3. Hedley, A. J., Fleming, C. J., Chesters, M. I., Michie, W., Crooks, J. Br.
med. J. 1970, i, 519. 4. Hedley, A. J., Scott, A. M., Debenham, G. Meth. Inf. Med. 1969, 8, 67. 5. Thjodleifsson, B., Hedley, A. J., Donald, D., Chesters, M. I., Kjeld, M., Beck, J. S., Crooks, J., Michie, W., Hall, R. Clin. Endocr. 1977, 7, 377. 6. Hedley, A. J., Ross, I. P., Beck, J. S., Donald, D., Albert-Recht, F., Michie, W., Crooks, J. Br. med. J. 1971, ii, 258.
roid disease seems low. 7-9Is the frequency of lasting remission after surgical treatment of hyperthyroidism different from that in Whiteq)
Department of Community Health, University Hospital and Medical School, Nottingham Department of Medicine, Gardiner Institute,
Western Infirmary,
A.
J. HEDLEY
Glasgow
R. E. YOUNG
Landspitalinn, Reykjavik, Iceland
B.
THJODLEIFSSON
POLYINOSINIC-POLYCYTIDYLIC ACID TREATMENT OF NEUROPATHY
SIR,--A patient with chronic relapsing polyneuropathy, probably dysimmune, has responded remarkably to treatment with polyinosinic-polycytidylic acid pOly-L-lysine stabilised with carboxymethyl cellulose (poly-l.c.L.C.). Poly-i.c.L.c. induces interferon in primates.’2 We have been using it in amyotrophic lateral sclerosis (A.L.S.) because of the possibility (unproved) that this disease has a chronic viral aetiology. While not of benefit in two A.L.S. patients (on no other therapy) treated weekly or twice weekly for 14 and 10 weeks at intravenous doses raised to 270 and 210 g/kg, respectively, the drug did elicit
an
influenza-like syndrome with infusion,
consisting of fever, chills, headache, and malaise for 4-12 h, and leucocyte changes (see below). S.G.P.T. frequently and S.G.O.T. very rarely were raised 2 1 1-1 fold for 3-5 days, but other laboratory tests, including liver function, serum-creatine-phosphokinase, and blood picture were unchanged. A 29-year-old man, known to us for 2 years, has had severe motor neuropathy of upper and lower limbs for 14 years. It had a subacute onset at age 15 and progressed over 3 months to wheelchair confinement, the patient being unable to feed himself. After 6 more months, some improvement began and continued for 11 years, initially in relation to 6-8 months of monthly corticotrophin treatment (A.C.T.H.). That improvement was slight; he could partially dress himself and walk with difficulty. The patient had two more severe exacerbations, at ages 26 and 28, one on no treatment and the other on prednisone 100 mg single-dose, alternate-day therapy, partial responses having followed A.C.T.H. given for 4 and 2 weeks. That last incomplete response then was treated partially but still unsatisfactorily with high single-dose daily prednisone for 8 at the end of which the third severe exacerbation occurred and was unresponsive to 9ymonths of azathioprine 3 mg/kg added to the prednisone dosage which had been reduced to 80 and 2.5 mg single doses on alternate days. Before the last two exacerbations motor conduction velocity was 34 m/s in the median nerve and 21 in the ulnar; cerebrospinal-fluid protein was 65 mg/dl, and with the last relapse it was 105. At that point the patient was very weak, unable to turn over in bed, stand alone, or walk (he used an electric wheelchair), or raise both arms to shoulder height. Because the patient improved temporarily during and for a few days after each influenza-like illness and because this apparently safe syndrome was provoked transiently by polyI.C.L.C. in our A.L.S. patients, we tried poly-I.c.L.c., 100 µg/kg by intravenous infusion over 30 min, once weekly, for 7 weeks to date. His prednisone remained unchanged at 80 and 2.5 mg on alternate days, and azathioprine was withdrawn. With each dose of poly-I.c.L.c. the patient had the usual transient ’flulike effects and transaminase changes noted above. 48 h after the first POlY-I.C.L.C. treatment the patient noted slight im-
months,
7. McGill, P. E. ibid. p. 679. 8. Gelfand, M. C. Afr. J. Medi. 1962, 8, 123. 9. Shee, J. C., Houston, W. ibid. 1963, 9, 267. 1. Levy, H. B., Baer, G., Barron, S., Buckler, C. E., Gibbs, C. J., Iadarola, M. J., London, W. T., Rice, J. J. infect. Dis. 1975, 132, 434. 2. Levine, A. S., Sivulich, M., Wiernick, P., Levy, H. B. Proc. Am. Ass. Cancer Res. (in the press).
positive findings. We share the scepticism of Candelaresi and hope that others will confirm or refute our results. Medizinische Klinik, Stadtspital Triemli Zürich, 8063 Zürich, Switzerland
et
al.
A. L. BLUM
PURPLE URINE BAGS
SIR,-A similar incident to that described by Mr Barlow and Mr Dickson (Jan. 28, p. 220) happened in this hospital when, for a day or two, the plastic urine bag and urine from an incontinent, elderly patient were noted to be bright purple. At first we thought that the colour was due to cutaneous absorption of coal-tar ointment (given for extensive psoriasis) but then similar, albeit less striking discoloration of urine and urine bag was noted in another elderly patient not on this treatment.
On
spectral analysis
of the urine
we
found, unlike Barlow
and Dickson, a peak at 520 nm in chloroform solution with no shoulder at 600 nm. Furthermore in patients with contaminated bowel syndrome or tropical sprue indicanuria is common, but these urines (after treatment with an oxidising agent) show a peak at 600 nm when extracted in chloroform. We are therefore not convinced that in our patient the colour was due to indigo (produced by oxidation of indican). Perhaps the purple colour we observed resulted from exposure of urine to a contaminant in the plastic catheter bag rather than from exposure to air. Certainly indicanuria in patients with contaminated bowel syndrome or tropical sprue leads to a blue colour only when the urine is treated with an oxidising agent such as sodium hypochlorite powder). Similarly traces of bleaching agents may also be important in producing the blue discoloration (due to indigo) in the rare blue diaper syndrome.1
(bleaching
Departments
of Clinical
Chemistry
and Thoracic Medicine, East Birmingham Hospital, Birmingham B9 5ST
H. G. SAMMONS C. SKINNER J. FIELDS
SIR,-Purple discolouration of urine bags is well-recognised anecdotal basis in geriatric units, and in the past 2 years we have seen four such cases in Cambridge. All were women, aged 79-97 (mean 87), with indwelling urinary catheters; all were poorly ambulant or chair-fast continuing-care patients on an
with moderate to severe dementia. We have examined our most recent case and find the blue pigment’s organic solubility as described by Mr Barlow and Mr Dickson. Its spectroscopic behaviour is also similar-i.e., a peak at 550 nm and a subsidiary peak at approximately 600 nm.
The idea that constipation is the primary mechanism for excessive indoxyl-sulphate production is attractive since these elderly patients have much prolonged gut transit-times.2 However, if this is the explanation why is the colour reaction not universal in such patients rather than just an occasional curiosity ? Associated urinary alkalinity favours indigo deposition,3 and all our patients had chronic urinary-tract infections with Pseudomonas ceruginosa alone or mixed with Proteus spp. While investigating this subject we found that indigo as a cause of blue urine was well described as long ago as 1857.’* Department of Geriatric Medicine, Chesterton Hospital, Cambridge CB4 1PT
BRIAN PAYNE
Department of Clinical Biochemistry, Addenbrooke’s Hospital, Cambridge CB2 2QR
ANDREW GRANT
1. Drummond, K. N.,
Alfred, F. M., Ulstrom, R. A., Good, R. A. Am. J. Med. 1964, 37, 928. 2. Brocklehurst, J. C., Kahn, M. Y. Geront. clin. 1969, 11, 293. 3. Harrison, G. A. Chemical Methods in Clinical Medicine; p. 73. London, 1949. 4.
Golding Bird. Urinary Deposits: their Diagnosis, Pathology and Therapeutical Indications; p. 331. London, 1857.
BACTERIAL CONTAMINATION OF THE SMALL BOWEL IN THE ELDERLY
SIR The relevance, diagnosis, and treatment of bacterial contamination of the upper small bowel evokes continued interest. Roberts et al.’ suggest that bacterial colonisation of the upper small bowel may produce non-specific symptoms unrelated to the gut and may occur in the elderly in the absence of the usually associated conditions-small-bowel stasis, blind loop, or abnormal immunological mechanisms. They suggest that the 14C-glycine-glycocholic-acid (G.C.A.) breath test is adequate for diagnosis and that the symptoms are readily relieved by treatment with broad-spectrum antibiotics. We too have encountered small-bowel colonisation in the elderly in the absence of gastrointestinal disease, illustrated by the three cases described below, but have reached different conclusions. A 77-year-old man was referred for investigation with an 18-month history of diarrhoea associated with urgency and occasional incontinence and 9 kg weight-loss. There were no other symptoms. X-ray investigation and mucosal biopsy showed no structural abnormality of the gastrointestinal tract and there was no biochemical or haematological evidence of malabsorption. A G.C.A. breath test was abnormal, and Staphylococcus aureus (107/ml), non-hæmolytic streptococci (107/ml), and enterococci (107/ml) were cultured from the jejunal aspirate. Treatment with ampicillin and co-trimoxazole produced no improvement in symptoms. Repeat jejunal culture showed colonisation with the same organism plus bacteroides (106/ml), but further treatment with antibiotics produced no improvement. A high-fibre diet produced a complete remission. A 63-year-old woman presented with tiredness, diarrhoea, and some weight-loss. There was no structural abnormality of the gastrointestinal tract on X-ray or mucosal biopsy. There was a minimal steatorrhoea (22.5 mmol/day) but all other tests for malabsorption were normal. Jejunal culture yielded enterococci (105/ml), Streptococcus viridans (104/ml), corynebacterium (105/ml), and fusobacterium (106/ml). Treatment with ampicillin and metronidazole followed by cephalexin and metronidazole did not improve symptoms although after treatment the jejunal aspirate was sterile. The symptoms eventually responded satisfactorily to aluminium hydroxide and chole-
styramine. A 93-year-old man presented with diarrhoea, weight loss, lethargy, and considerable malaise. Investigation revealed no structural abnormality of the gastrointestinal tract and no evidence of malabsorption. A G.C.A. breath test was abnormal; jejunal aspiration was unsuccessful. Treatment with co-trimoxazole produced some improvement in diarrhoea and general well-being which lasted for 2 months but recurrent symptoms were not controlled by further antibiotics. These three patients support the suggestion that there may be abnormal numbers of organisms in the small bowel of elderly patients who have none. of the usual conditions associated with bacterial contamination of the small bowel. Howpatients had diarrhoea and two complained of considerable tiredness, malaise, and weight-loss, the sort of symptoms emphasised by the Newcastle workers. Two of our patients had abnormal breath tests but we do not share the confidence of Roberts et al. in this test. Our experience with over 200 tests done concurrently with jejunal aspirates have shown such a high frequency of errors-30% false positive results in the presence of anaerobic organisms and 25% false negative results-that we feel the test is unhelpful diagnostically and no longer use it. The presence of abnormal smallbowel flora is clearly related to the clinical features of the classical blind-loop syndrome and antibiotic therapy brings clinical improvement. Our experience with patients like those described here and patients with previous gastric surgery and abnormal jejunal bacteriology has been that antibiotic therapy produces disappointing clinical results even though the upper small bowel may be sterilised. Bacterial culture is required for ever, all these
1.
Roberts, S. H., James, O., Jarvis, E. H. Lancet, 1977, ii, 1193.
503 the accurate diagnosis of small-bowel contamination in these patients and jejunal aspiration and culture with an open-ended tube is usually both simple and well tolerated. However, aspiration and culture of fasting gastric juice may suffice as an alternative as we have found that the results closely mirror those of small-bowel culture when the two examinations are
carried out concurrently. It seems that there are frequently abnormal numbers of bacteria in the upper small bowel in patients with a variety of general and gastrointestinal complaints and who are either old, have gastric achlorhydria, or have had peptic-ulcer surgery. However, the relationship of these bacteria to the clinical problem is conjectural and will be clarified only by further studies with accurate ieiunal bacteriolosv.
Gastrointestinal Centre, Southern General Hospital, Glasgow G514TF
R. J. HOLDEN P. MILLS L. CRAIG J. D. SLEIGH I. MACKENZIE W. WATSON G. WATKINSON G. P. CREAN
POST-THYROIDECTOMY THYROTOXICOSIS
SIR, The study reported by Dr Kalk and his colleagues (Feb. 11, p. 291) confirms previous reports that post-thyroidectomy recurrent hyperthyroidism occurs in varying but often large numbers of patients and re-emphasises the need for longterm surveillance in chronic disease, including late-onset recurrences or thyroid failure after treatment of hyperthyroidism.2.3 The studies Kalk et al. cite are of prevalence (not incidence), and are inevitably based on retrospective examination of survivors of those treated; the risk of recurrent hyperthyroidism will only be determined by measuring its incidence in longitudinal studies in defined patient groups. Such a plan for life-long follow-up, implemented in 1968,4 is now being evaluated by, for example, life-table techniques to estimate the cumulative probability of events such as recurrence and hypothyroidism after destructive therapy for hyperthyroidism. Kalk et al. refer to our studies5 on factors determining the long-term response to subtotal thyroidectomy but do not emphasise that environmental factors, such as dietary iodine and the variation in levels of autoimmune thyroiditis in different populations, may together be more important as determinants of recurrences than is remnant size alone. Comments on the relation between remnant size and outcome of surgery in different centres are probably meaningless unless they are accompanied by estimates of both the frequency and severity of thyroiditis in the gland and of the proportion of postoperative patients in whom the underlying disease remains active.6 Such activity may be identified by T3 suppression or T.R.H. stimulation tests (although there is disagreement about the comparability of the two techniques) and probably represent the only subgroup at risk of recurrent hyperthyroidism. Large remnants will never cause a recurrence in those patients in whom the extrapituitary stimulus to the gland has remitted and similarly a small remnant may not prevent it in those in whom the stimulus persists. Over one quarter of the Johannesburg patients were Black Africans in whom the frequency of autoimmune types of thy1.
Small,
w. r.
Lancet, 1967, i, 997.
2. Crooks, J. in Computers in the Service of Medicine (edited by G. McLachlan and R. A. Shegog) Nuffield Provincial Hospitals Trust, 1968. 3. Hedley, A. J., Fleming, C. J., Chesters, M. I., Michie, W., Crooks, J. Br.
med. J. 1970, i, 519. 4. Hedley, A. J., Scott, A. M., Debenham, G. Meth. Inf. Med. 1969, 8, 67. 5. Thjodleifsson, B., Hedley, A. J., Donald, D., Chesters, M. I., Kjeld, M., Beck, J. S., Crooks, J., Michie, W., Hall, R. Clin. Endocr. 1977, 7, 377. 6. Hedley, A. J., Ross, I. P., Beck, J. S., Donald, D., Albert-Recht, F., Michie, W., Crooks, J. Br. med. J. 1971, ii, 258.
roid disease seems low. 7-9Is the frequency of lasting remission after surgical treatment of hyperthyroidism different from that in Whiteq)
Department of Community Health, University Hospital and Medical School, Nottingham Department of Medicine, Gardiner Institute,
Western Infirmary,
A.
J. HEDLEY
Glasgow
R. E. YOUNG
Landspitalinn, Reykjavik, Iceland
B.
THJODLEIFSSON
POLYINOSINIC-POLYCYTIDYLIC ACID TREATMENT OF NEUROPATHY
SIR,--A patient with chronic relapsing polyneuropathy, probably dysimmune, has responded remarkably to treatment with polyinosinic-polycytidylic acid pOly-L-lysine stabilised with carboxymethyl cellulose (poly-l.c.L.C.). Poly-i.c.L.c. induces interferon in primates.’2 We have been using it in amyotrophic lateral sclerosis (A.L.S.) because of the possibility (unproved) that this disease has a chronic viral aetiology. While not of benefit in two A.L.S. patients (on no other therapy) treated weekly or twice weekly for 14 and 10 weeks at intravenous doses raised to 270 and 210 g/kg, respectively, the drug did elicit
an
influenza-like syndrome with infusion,
consisting of fever, chills, headache, and malaise for 4-12 h, and leucocyte changes (see below). S.G.P.T. frequently and S.G.O.T. very rarely were raised 2 1 1-1 fold for 3-5 days, but other laboratory tests, including liver function, serum-creatine-phosphokinase, and blood picture were unchanged. A 29-year-old man, known to us for 2 years, has had severe motor neuropathy of upper and lower limbs for 14 years. It had a subacute onset at age 15 and progressed over 3 months to wheelchair confinement, the patient being unable to feed himself. After 6 more months, some improvement began and continued for 11 years, initially in relation to 6-8 months of monthly corticotrophin treatment (A.C.T.H.). That improvement was slight; he could partially dress himself and walk with difficulty. The patient had two more severe exacerbations, at ages 26 and 28, one on no treatment and the other on prednisone 100 mg single-dose, alternate-day therapy, partial responses having followed A.C.T.H. given for 4 and 2 weeks. That last incomplete response then was treated partially but still unsatisfactorily with high single-dose daily prednisone for 8 at the end of which the third severe exacerbation occurred and was unresponsive to 9ymonths of azathioprine 3 mg/kg added to the prednisone dosage which had been reduced to 80 and 2.5 mg single doses on alternate days. Before the last two exacerbations motor conduction velocity was 34 m/s in the median nerve and 21 in the ulnar; cerebrospinal-fluid protein was 65 mg/dl, and with the last relapse it was 105. At that point the patient was very weak, unable to turn over in bed, stand alone, or walk (he used an electric wheelchair), or raise both arms to shoulder height. Because the patient improved temporarily during and for a few days after each influenza-like illness and because this apparently safe syndrome was provoked transiently by polyI.C.L.C. in our A.L.S. patients, we tried poly-I.c.L.c., 100 µg/kg by intravenous infusion over 30 min, once weekly, for 7 weeks to date. His prednisone remained unchanged at 80 and 2.5 mg on alternate days, and azathioprine was withdrawn. With each dose of poly-I.c.L.c. the patient had the usual transient ’flulike effects and transaminase changes noted above. 48 h after the first POlY-I.C.L.C. treatment the patient noted slight im-
months,
7. McGill, P. E. ibid. p. 679. 8. Gelfand, M. C. Afr. J. Medi. 1962, 8, 123. 9. Shee, J. C., Houston, W. ibid. 1963, 9, 267. 1. Levy, H. B., Baer, G., Barron, S., Buckler, C. E., Gibbs, C. J., Iadarola, M. J., London, W. T., Rice, J. J. infect. Dis. 1975, 132, 434. 2. Levine, A. S., Sivulich, M., Wiernick, P., Levy, H. B. Proc. Am. Ass. Cancer Res. (in the press).
