- Email: [email protected]
ARTHROPATHIES AND PARROTS
93
Neither injection nor surgery is effective for all patients. Each patient should be treated according to specific indications. In this way, excellent results will be obtained, both from injection therapy and surgery. ROBERT A. NABATOFF 1020 Park Avenue, DAVID C. C. STARK. New York, N.Y. 10028, U.S.A. ARTHROPATHIES AND PARROTS SIR,-It is well known that parrots, though capable of learning and repeating, must be programmed selectively lest their lack of inhibition leads to embarrassment. We therefore hasten to correct the mistaken impression given by your review (June 23, p. 1424) of our book, Joint Disease; All The Arthropathies. We would not advise any candidate for membership of the Royal College of Physicians to memorise the facts about o’nyong nyong, acanthocheilonema perstans, or the Maroteux-Lamy syndrome any more than a traveller on the train would memorise the time-table or a telephone subscriber the directory. Rather we hope that a general practitioner, as well as a rheumatic or any other specialist, will find, when faced with an odd arthropathy, that he can look it up. For this reason, we have put the maximum information into the minimum space, and there are few verbs, many nouns, no illustrations, and no funny stories. So heaven help the digestion of any parrots who try to subsist on this diet. St. Bartholomew’s Hospital, London EC1A 7BE.
E. C. HUSKISSON.
Westminster Hospital, London SW1P 2AP.
F. DUDLEY HART.
BACLOFEN AND LITHIUM IN HUNTINGTON’S CHOREA
SIR,-Two articles have described post-mortem findings of low
y-aminobutyric acid (G.A.B.A.) levels1 and reduced activity of glutamic-acid decarboxylase2 in the basal ganglia in Huntington’s chorea (H.c.). Baclofen (’ Lioresal ’), &bgr;-p-chlorophenyl-&ggr;-aminobutyric acid, is a derivative of G.A.B.A., which penetrates the blood/brain barrier and may act like G.A.B.A. in the central nervous system. Furthermore, the impulse flow in dopamine nerves may be inhibited by baclofen, to judge from our preliminary animal experiments. We have tried baclofen in two female patients with H.c., aged 57 and 69, and with choreic symptoms of 7 and 15 years’ duration. Before the trial the younger patient was taking imipramine 75 mg., clopenthixol 15 mg., and chlorpromazine 25 mg. daily, and the older patient was on 225 mg. of thioridazine. This was not changed, and baclofen was started in daily doses of 15 mg. The dosage was then gradually increased, reaching 90 mg. 15 days after the start. There was a slight improvement in both patients, beginning approximately at the 60 mg. level, with a decreasing intensity of the choreic movements, but little change in frequency. At 90 mg. the patients became drowsy, and baclofen was not increased further. Lithium was added on day 22 in doses adjusted to get a serum level of 0’5-1 meq. per litre. A third female patient, aged 42,
was now
started
on
baclofen. Her symptoms of
H.c. were of more than 10
years’ duration, but she was greatly improved on lithium and 4 mg. of haloperidol for 6 months (one of the cases reported by one of us 3). Within a few days this patient (on 30 mg. of baclofen) and the woman of 57 showed a severe aggravation of their hyperkinetic symptoms, suggesting an interaction of baclofen and lithium. Baclofen
was
therefore discontinued in all
1.
Perry, T. L., Hansen, S., Kloster, M. New Engl. J. Med. 1973, 288,
2. 3.
Mackay, A. V. P., Rayner, C. N., Iversen, L. L. Lancet, 1973, i, 1090. Dalén, P. ibid. p. 107.
337.
three cases on the 27th day of the trial, and in about 3 days the signs of this interaction had disappeared. The first two patients were further improved on lithium and increased doses of neuroleptics. We should like to thank Dr J. Wålinder for a patient under his care.
permission
to
study
Department of Pharmacology, University of Göteborg, S-40033 Göteborg 33, Sweden. St. Jörgen’s Hospital, S-42203 Hisings Backa, Sweden. Sahlgren Hospital, S-41345 Göteborg, Sweden.
NILS-ERIK ANDÉN. PER DALÉN.
BARBRO JOHANSSON.
SELECTIVE TRANSFORMATION OF B LYMPHOCYTES BY E.B. VIRUS SIR,-The findings of Dr Sheldon and his colleagues1 that the atypical lymphocyte of infectious mononucleosis is derived from the T-lymphocyte population is of great interest, since our findings, briefly described here, demonstrate that the agent of infectious mononucleosis (E.B. virus)2 permanently transforms (i.e., confers the ability to grow continuously in vitro) only lymphocytes with B-cell characteristics. We have studied in-vitro E.B.-virus transformation of fetal thymocytes, purified human peripheral lymphoid cells obtained from umbilical-cord blood, and peripheral lymphocytes from an adult patient with agammaglobulinaemia. An E.B.-virus producing lymphoid cell line established from a patient with infectious mononucleosis was used as a virus source. These lymphoid cell populations were monitored for B and T lymphocyte percentages before and after infection with E.B. virus. These markers included for B cells: complement receptors,surface immunoglobulin,4and cytotoxic antisera 5; and for T cells: sheep red-blood-cell receptors 6 and cytotoxic antisera.’ The results were: Percentages of Band T cell markers on human lymphoid cells before and after transformation by E.B, virus
Most continuous lymphoid-cell lines have B-cell characteristics8 and have been found to consistently contain the E.B.-virus genome.9,10 Molt-4, however, a continuous lymphoid cell line with T-cell characteristics," does not contain the E.B.-virus genome. 12 These observations, plus the findings reported here, strongly suggest P. J., Hemsted, E. H., Papamichail, M., Holborow, E. J. Lancet, 1973, i, 1153. 2. Henle, G., Henle, W., Diehl, V. Proc. natn. Acad. Sci. U.S.A. 1968, 59, 94. 3. Bianco, C., Patrick, T., Nussenzweig, V. J. exp. Med. 1970, 132, 702. 4. Rabellino, E., Colon, S., Grey, H. M., Unanue, E. R. ibid. 1971, 133, 1.
Sheldon,
5.
Smith, R. W., Glaze, R. N., Hathcock, K. S., Edelson, R. Proceedings of 8th Leucocyte Culture Conference (in the press). Lay, W. H., Mendes, N. F., Bianco, W., Nussenzweig, V. Nature, 1971, 230, 531. Smith, R. W., Terry, W. D., Buell, D. N., Sell, K. W. J. Immun. 1973, 110, 884. Moore, G. F., Minowada, J. New Engl. J. Med. 1973, 288, 106. ZurHausen, H., Scholte, Holthausen, H. Nature, 1970, 227, 245. Nonoyama, J., Pagano, J. Nature New Biol. 1971, 223, 103. Minowada, J., Ohnuma, T., Moore, G. E. J. natn. Cancer Inst. 1972, 49, 891. Nonoyama, M. Personal communication.
156.
6.
7. 8. 9. 10. 11. 12.
Neither injection nor surgery is effective for all patients. Each patient should be treated according to specific indications. In this way, excellent results will be obtained, both from injection therapy and surgery. ROBERT A. NABATOFF 1020 Park Avenue, DAVID C. C. STARK. New York, N.Y. 10028, U.S.A. ARTHROPATHIES AND PARROTS SIR,-It is well known that parrots, though capable of learning and repeating, must be programmed selectively lest their lack of inhibition leads to embarrassment. We therefore hasten to correct the mistaken impression given by your review (June 23, p. 1424) of our book, Joint Disease; All The Arthropathies. We would not advise any candidate for membership of the Royal College of Physicians to memorise the facts about o’nyong nyong, acanthocheilonema perstans, or the Maroteux-Lamy syndrome any more than a traveller on the train would memorise the time-table or a telephone subscriber the directory. Rather we hope that a general practitioner, as well as a rheumatic or any other specialist, will find, when faced with an odd arthropathy, that he can look it up. For this reason, we have put the maximum information into the minimum space, and there are few verbs, many nouns, no illustrations, and no funny stories. So heaven help the digestion of any parrots who try to subsist on this diet. St. Bartholomew’s Hospital, London EC1A 7BE.
E. C. HUSKISSON.
Westminster Hospital, London SW1P 2AP.
F. DUDLEY HART.
BACLOFEN AND LITHIUM IN HUNTINGTON’S CHOREA
SIR,-Two articles have described post-mortem findings of low
y-aminobutyric acid (G.A.B.A.) levels1 and reduced activity of glutamic-acid decarboxylase2 in the basal ganglia in Huntington’s chorea (H.c.). Baclofen (’ Lioresal ’), &bgr;-p-chlorophenyl-&ggr;-aminobutyric acid, is a derivative of G.A.B.A., which penetrates the blood/brain barrier and may act like G.A.B.A. in the central nervous system. Furthermore, the impulse flow in dopamine nerves may be inhibited by baclofen, to judge from our preliminary animal experiments. We have tried baclofen in two female patients with H.c., aged 57 and 69, and with choreic symptoms of 7 and 15 years’ duration. Before the trial the younger patient was taking imipramine 75 mg., clopenthixol 15 mg., and chlorpromazine 25 mg. daily, and the older patient was on 225 mg. of thioridazine. This was not changed, and baclofen was started in daily doses of 15 mg. The dosage was then gradually increased, reaching 90 mg. 15 days after the start. There was a slight improvement in both patients, beginning approximately at the 60 mg. level, with a decreasing intensity of the choreic movements, but little change in frequency. At 90 mg. the patients became drowsy, and baclofen was not increased further. Lithium was added on day 22 in doses adjusted to get a serum level of 0’5-1 meq. per litre. A third female patient, aged 42,
was now
started
on
baclofen. Her symptoms of
H.c. were of more than 10
years’ duration, but she was greatly improved on lithium and 4 mg. of haloperidol for 6 months (one of the cases reported by one of us 3). Within a few days this patient (on 30 mg. of baclofen) and the woman of 57 showed a severe aggravation of their hyperkinetic symptoms, suggesting an interaction of baclofen and lithium. Baclofen
was
therefore discontinued in all
1.
Perry, T. L., Hansen, S., Kloster, M. New Engl. J. Med. 1973, 288,
2. 3.
Mackay, A. V. P., Rayner, C. N., Iversen, L. L. Lancet, 1973, i, 1090. Dalén, P. ibid. p. 107.
337.
three cases on the 27th day of the trial, and in about 3 days the signs of this interaction had disappeared. The first two patients were further improved on lithium and increased doses of neuroleptics. We should like to thank Dr J. Wålinder for a patient under his care.
permission
to
study
Department of Pharmacology, University of Göteborg, S-40033 Göteborg 33, Sweden. St. Jörgen’s Hospital, S-42203 Hisings Backa, Sweden. Sahlgren Hospital, S-41345 Göteborg, Sweden.
NILS-ERIK ANDÉN. PER DALÉN.
BARBRO JOHANSSON.
SELECTIVE TRANSFORMATION OF B LYMPHOCYTES BY E.B. VIRUS SIR,-The findings of Dr Sheldon and his colleagues1 that the atypical lymphocyte of infectious mononucleosis is derived from the T-lymphocyte population is of great interest, since our findings, briefly described here, demonstrate that the agent of infectious mononucleosis (E.B. virus)2 permanently transforms (i.e., confers the ability to grow continuously in vitro) only lymphocytes with B-cell characteristics. We have studied in-vitro E.B.-virus transformation of fetal thymocytes, purified human peripheral lymphoid cells obtained from umbilical-cord blood, and peripheral lymphocytes from an adult patient with agammaglobulinaemia. An E.B.-virus producing lymphoid cell line established from a patient with infectious mononucleosis was used as a virus source. These lymphoid cell populations were monitored for B and T lymphocyte percentages before and after infection with E.B. virus. These markers included for B cells: complement receptors,surface immunoglobulin,4and cytotoxic antisera 5; and for T cells: sheep red-blood-cell receptors 6 and cytotoxic antisera.’ The results were: Percentages of Band T cell markers on human lymphoid cells before and after transformation by E.B, virus
Most continuous lymphoid-cell lines have B-cell characteristics8 and have been found to consistently contain the E.B.-virus genome.9,10 Molt-4, however, a continuous lymphoid cell line with T-cell characteristics," does not contain the E.B.-virus genome. 12 These observations, plus the findings reported here, strongly suggest P. J., Hemsted, E. H., Papamichail, M., Holborow, E. J. Lancet, 1973, i, 1153. 2. Henle, G., Henle, W., Diehl, V. Proc. natn. Acad. Sci. U.S.A. 1968, 59, 94. 3. Bianco, C., Patrick, T., Nussenzweig, V. J. exp. Med. 1970, 132, 702. 4. Rabellino, E., Colon, S., Grey, H. M., Unanue, E. R. ibid. 1971, 133, 1.
Sheldon,
5.
Smith, R. W., Glaze, R. N., Hathcock, K. S., Edelson, R. Proceedings of 8th Leucocyte Culture Conference (in the press). Lay, W. H., Mendes, N. F., Bianco, W., Nussenzweig, V. Nature, 1971, 230, 531. Smith, R. W., Terry, W. D., Buell, D. N., Sell, K. W. J. Immun. 1973, 110, 884. Moore, G. F., Minowada, J. New Engl. J. Med. 1973, 288, 106. ZurHausen, H., Scholte, Holthausen, H. Nature, 1970, 227, 245. Nonoyama, J., Pagano, J. Nature New Biol. 1971, 223, 103. Minowada, J., Ohnuma, T., Moore, G. E. J. natn. Cancer Inst. 1972, 49, 891. Nonoyama, M. Personal communication.
156.
6.
7. 8. 9. 10. 11. 12.