- Email: [email protected]
THE SIGNIFICANCE OF BRAIN-AMINE CONCENTRATIONS
596 in kittens by
hyperoxia even when the eyelids have not yet
CALCITONIN AND THYROTOXIC HYPERCALCÆMIA SiR,łThe report by Buckle et al.1 on the treatment of thyrotoxic hypercalcaemia with porcine calcitonin is an interesting confirmation of the effect of calcitonin in man. In addition, it supports the hypothesis that calcitonin is deficient in thyrotoxicosis. The role of calcitonin in the treatment of the patient reported may have been a little overstated, however. The patient was a very sick man with advanced thyrotoxicosis and myopathy, central-nervoussystem symptoms, and gastrointestinal symptoms. The severity of the thyrotoxicosis is evidenced by a serumprotein-bound-iodine of more than 15 µg. per 100 ml., a pulse-rate of 160, and his inability to stand unaided. His temperature was not stated but if it was raised he would fit all the criteria of thyrotoxic crisis.2-4 His moderate hyper-
Recent work on the effect of light on the retina suggests that its injurious effect is confined to the outer layers, leading to degeneration of the visual cells, but the inner layers, wherein the retinal vessels develop, are unaffected. There is, therefore, no experimental evidence that light can destroy growing retinal vessels. The work of Dr. Riley and Dr. Slater is certainly of interest and worth pursuing, but the significance of their speculations should be considered in the context of other published work. Department of Physiology and Biochemistry, Institute of Ophthalmology, CLIVE GRAYMORE. London W.C.1.
calcasmia of 14.2 mg. per 100 ml. may have contributed to gastrointestinal symptoms, but this is by no means the
THE SIGNIFICANCE OF BRAIN-AMINE
opened.
his
only possible explanation for them.55 Buckle et al.l leave the impression that the reduction of hypercalcaemia is a major consideration in the treatment of thyrotoxicosis. This is not generally true, nor indeed does their case-reportsupportthisproposition. BaxterandBondy 6 found that approximately 20% of hyperthyroid patients have hypercalcasmia and in none of these was reduction of serum-calcium necessary as emergency treatment. Treatof severe thyrotoxicosis should be directed toward the cause of the condition-the overactive thyroid gland, plus the life-threatening sequels of the disease including hyperment
pyrexia, circulatory failure, infection, and, possibly, adrenal insufficiency. Eugene Hospital and Clinic, Eugene Oregon 97401, U.S.A.
BYRON U. MUSA.
PATHOGENESIS OF RETROLENTAL FIBROPLASIA letter SiR,łThe by Dr. Riley and Dr. Slater (Aug. 2, a p. 265) suggesting possible mechanism for the cause of retrolental fibroplasia (R.L.F.) is of considerable interest. Apart from the immediate concern of reducing still further the incidence of this condition in premature babies, the implications are even more widespread in terms of tissue growth and regeneration in general. I agree, however, with the objections raised by Dr. Forrester and Dr. Roberton (Aug. 16), and I doubt the wisdom of putting academic argument into practice at this stage. Unfortunately, Dr. Riley and Dr. Slater seem to be unaware of the extent of the work done at this institute by Prof. Norman Ashton and his colleagues. These studies, reinforced by extensive experimental work in other centres, established oxygen as the primary cause of R.LF., and thus led directly to a considerable control of this disease. Careful investigations spanning more than a decade eliminated many other factors. Indeed, the suggestion that the exposure of immature eyes to light might be a precipitating factor in retrolental fibroplasia is certainly not novel; it was one of the earliest possibilities to be investigated, and with negative results.’ The basis of the pathogenesis of R.L.F. is now known to be the specific destructive effect of oxygen on growing retinal vessels, and this can be produced 1.
Buckle, R. M., Mason,
A. M.
S., Middleton, J. E. Lancet, 1969, i,
1128. 2. 3. 4. 5. 6. 7.
McArthur, J. W., Rawson, R. W., Means, J. H., Cope, O. J. Am. med. Ass. 1947, 34, 868. Waldstein, S. S., Slodki, S. J., Kagniec, G. I., Bronsky, D. Ann. intern. Med. 1960, 52, 626. Lamberg, S. A. Acta med. scand. 1959, 164, 479. Clerkin, E. P., Murphy, R. Med. Clins N. Am. 1966, 50, 569. Baxter, J. D., Bondy, P. K. Ann. intern. Med. 1966, 65, 429. Zacharias, L. Am. J. Ophthal. 1952, 35, 1426.
CONCENTRATIONS SiR,łDr. Shaw (Aug. 9, p. 320) drew attention to the three studies which have compared amine levels in the brainstems of patients who had committed suicide with those in patients who died of other causes. He believes that further studies are indicated since these results suggest a decline in the concentrations of 5-hydroxyindoles in the brainstems of endogenously depressed suicides. However, since no firm conclusions can be drawn from the inconsistent results of these reports, I suggest that we must obtain more information about the many variables affecting amine concentrations, if there is to be any further gain from a repetition of this kind of investigation. If we examine the mean amine levels and standard deviations (s.D.) of the control groups in the previous studies (including that of Maclean et al.1), it can be seen that there is considerable variation in the mean levels of 5-hydroxytryptamine (5-H.T.), and in the individual levels for both 5-H.T. and 5-hydroxyindoleacetic acid (5-H.I.A.A.) in each group.
Figures in parentheses show the number of specimens. Some of the variables which may have contributed to these differences include the terminal illnesses, the age and sex of the patients, any previous drug treatment, the rapidity of death, the time between death and necropsy, the dissection of the specimens, and the methods of assay. All these have been considered in the previous reports, but more detailed studies are needed. Unless the assays are carried out immediately after the
necropsies, another variable is the period of storage while deep-frozen, between necropsy and assay. In addition, even after just a few hours of storage in dry ice, any partial thawing that occurs before homogenisation may also affect the amine levels.5 Dr. Shaw states that the data of Bourne et al.3 are not reliable because of the long periods of storage involved, and because the mean storage time for the controls was longer than that of the suicide group. Since this storage variable is also relevant in the work of Shaw et al.,2 the results of a study in which I investigated the effect of different periods of storage may be of interest. Maclean, R., Nicholson, W. J., Pare, C. M. B., Stacey, R. S. Lancet, 1965, ii, 205. 2. Shaw, D. M., Camps, F. E., Eccleston, E. Br. J. Psychiat. 1967, 113, 1407. 3. Bourne, H. R., Bunney, W. E., Colburn, R. W., Davis, J. M., Davis, J. N., Shaw, D. M., Coppen, A. J. Lancet, 1968, ii, 805. 4. Pare, C. M. B., Yeung, D. P. H., Price, K., Stacey, R. S. Lancet, July 19, 1969, p. 133. 5. Joyce, D. Br. J. Pharmac. Chemother. 1962, 18, 370. 1.
597 A minimum of three brainstem specimens from unwere assayed after storage at -17°C, in sealed plastic bags, for 1, 2, 4, 5, 8, 12, 26, 54, and 75 days after necropsy. After precipitation of protein with zinc sulphate, the 5-H.T. was assayed by the method of Kurtzman et al., modified by the addition of two borate-buffer washes to the ’butanol extract, and the 5-H.I.A.A. was assayed by Ashcroft and Sharman’s method,’ modified by the use of ethyl acetate for the extraction. Internal standards of 5-H.T. and 5-H.I.A.A. were used. The means of the 5-H.T. and 5-H.I.A.A. concentrations were taken after each period of storage, and the following results were obtained: (1) There were significant falls in the mean concentrations of both 5-H.T. (p < 0.01) and 5-H.I.A.A. (p < 0’02) between 1 and 26 days’ storage. Both these falls were of exponential type, levelling off at about 20-25 days. Concentrations after. 54 and 75 days’ storage indicated little subsequent
selected necropsies
change up to 75 days, but longer periods of storage (as cannot
further changes during even in the work of Bourne et al.3)
be ruled out.
(2) On the assumption that the falls were exponential, analysis of all the results gave the following estimated mean
concentrations:
Thus the falls during the first 20-25 days of storage were 34% of the 5-H.T. and 44% of the 5-H.I.A.A. (3) The mean concentrations of the 14 specimens assayed within 5 days of necropsy (mean, 3 days) were: 5-H.T. 550 ng./g., S.D. 93; 5-H.I.A.A. 2830 ng./g., S.D. 948. After allowing for a comparable storage time, the mean concentrations which were found for both 5-H.T. and 5-H.I.A.A. are much higher than those in any of the previous studies. This widens still further the range of mean concentrations which has been found in control groups. The characteristics of the decay process of these amines must depend on such factors as their distribution and routes of degradation, so it is possible that any changes in 5-H.T. metabolism associated with some forms of depressive illness may influence the decay process during storage. It is therefore planned to make a comparison between the decays of a control group and a suicide group, which may indicate changes in amine distribution and routes of degradation which would not necessarily be associated with changes in the amine concentrations. I should like to thank Dr. G. W. Ashcroft for his help and advice. M.R.C. Brain Metabolism Unit, University Medical School, and The Royal Edinburgh Hospital,
Edinburgh.
J. H. DOWSON.
ISCHÆMIC HEART-DISEASE AND THE NEPHROTIC SYNDROME SIR,-Dr. Berlyne and Dr. Mallick (Aug. 23, p. 399) have helped greatly by beginning to collect some facts about the vexed question of ischaemic heart-disease in the nephrotic syndrome. They believe, because of the risk, that " it is essential to use not only steroids but also immunosuppressive agents ". This advice seems debatable, but if it is to be followed it would seem wise to start a prospective registry to record tumours and genetic abnormalities arising in these their progeny, since numbers of young adults will be involved. If this is not done there might be an unusually prolonged " phase of illusion " with immunosuppressive treatment, for the immediate benefits might
patients
or
6.
Kurtzman, R., Shore, P. A., Bogdanksi, D., Brodie, B.
7.
Ashcroft,
J.
Neurochem. 1961, 6, 226. G. W., Sharman, D. F. Br. J. Pharmac. Chemother.
1962, 19, 153.
antecede the disadvantages of the interval.
treatment
Department of Pharmacology and Therapeutics, London Hospital Medical College, E.1.
by
a
long
D. W. VERE.
GENETIC PUNCTUATION SIGNALS SIR,-We should like to comment on Dr. Carter’s third article-" The Genes."1 In discussing the punctuation signals in the genetic code, Dr. Carter mentions the codons UAA, UAG, and UGA as possible signals for beginning and ending polypeptide chains. Studies on Escherichia coli have shown that initiation of protein synthesis is a complex phenomenon involving at least three ribosomal factors, and a particular species of transferR.N.A. (formyl-methionyl-tR.N.A.) which recognises the codon AUG as an initiation signal.2 Many bacteria and bacterial viruses have been shown to utilise this mechanism. Again in E. coli, the codons UAA, UAG, and UGA can serve as signals for chain termination.3 Again special adaptor molecules are involved in the recognition of these codons, in this case proteins, release-factor 1 which recognises UAA and UAG, and release-factor 2 which recognises UAA and UGA.4 5 In higher organisms-especially mammals-there is little information on the mechanisms of initiation and termination. As yet, no patricular adaptor molecules have been shown to play a part in the mechanisms of starting and stopping. Indirect evidence, however, suggests that the termination signals may be the same.67 We hope that future research will provide information on the punctuation mechanisms in mammalian systems, and add to the knowledge of mammalian genetics which Dr. Carter has so thoroughly reviewed. of Biochemical Genetics, National Institutes of Health,
Laboratory
Bethesda, Maryland.
E. M. SCOLNICK C. T. CASKEY.
TELEVISION TEACHING to the teaching of clinical medicinehas been tested in Africa 9 and in American centres.1o In the Uganda trial, using crossover control groups, similar conclusions to those of the Glasgow groups were reached-namely, that television teaching was as efficient as a standard lecture demonstration. In this instance the teaching was presented " live ", with a two-way audio-system, so that it was possible to maintain contact with the audience and therefore achieve a more flexible presentation guided by the reactions of the audience. Videotape recordings and films do not have this flexibility, but can provide a carefully planned demonstration with a full " supporting cast " of visual aids capable of storage for future occasions. This is of particular value in Britain where patients with classical physical signs are not so readily available for teaching sessions. A major advantage of television over lecture-
SiR,ńThe application of television
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Carter, C. O. Lancet, 1969, i, 1087. Iwasaki, K., Sabol, S., Wahba, A. J., Ochoa, S. Archs Biochem. Biophys. 1968, 125, 542., Caskey, C. T., Tompkins, R., Scolnick, E., Caryk, T., Nirenberg, M. Science, N.Y. 1968, 162, 135. Scolnick, E., Tompkins, R., Caskey, T., Nirenberg, M. Proc. natn. Acad. Sci. 1968, 61, 768. Milman, G., Goldstein, J., Scolnick, E., Caskey, T. ibid. (in the press). Caskey, C. T., Beaudet, A., Nirenberg, M. J. Molec. Biol. 1968, 37, 99. Gupta, N. K. J. biol. Chem. 1968, 243, 4959. Kenmure, A. C. F., Thomson, G. O. B., Kennedy, R. D., Cameron, A. J. V. Lancet, Aug. 23, 1969, p. 425. Cantrell, E. G., Craven, J. L. Br. J. med. Educ. 1969, 3, 110. Ramey, J. W. J. med. Educ. 1964, 39, 1107.
hyperoxia even when the eyelids have not yet
CALCITONIN AND THYROTOXIC HYPERCALCÆMIA SiR,łThe report by Buckle et al.1 on the treatment of thyrotoxic hypercalcaemia with porcine calcitonin is an interesting confirmation of the effect of calcitonin in man. In addition, it supports the hypothesis that calcitonin is deficient in thyrotoxicosis. The role of calcitonin in the treatment of the patient reported may have been a little overstated, however. The patient was a very sick man with advanced thyrotoxicosis and myopathy, central-nervoussystem symptoms, and gastrointestinal symptoms. The severity of the thyrotoxicosis is evidenced by a serumprotein-bound-iodine of more than 15 µg. per 100 ml., a pulse-rate of 160, and his inability to stand unaided. His temperature was not stated but if it was raised he would fit all the criteria of thyrotoxic crisis.2-4 His moderate hyper-
Recent work on the effect of light on the retina suggests that its injurious effect is confined to the outer layers, leading to degeneration of the visual cells, but the inner layers, wherein the retinal vessels develop, are unaffected. There is, therefore, no experimental evidence that light can destroy growing retinal vessels. The work of Dr. Riley and Dr. Slater is certainly of interest and worth pursuing, but the significance of their speculations should be considered in the context of other published work. Department of Physiology and Biochemistry, Institute of Ophthalmology, CLIVE GRAYMORE. London W.C.1.
calcasmia of 14.2 mg. per 100 ml. may have contributed to gastrointestinal symptoms, but this is by no means the
THE SIGNIFICANCE OF BRAIN-AMINE
opened.
his
only possible explanation for them.55 Buckle et al.l leave the impression that the reduction of hypercalcaemia is a major consideration in the treatment of thyrotoxicosis. This is not generally true, nor indeed does their case-reportsupportthisproposition. BaxterandBondy 6 found that approximately 20% of hyperthyroid patients have hypercalcasmia and in none of these was reduction of serum-calcium necessary as emergency treatment. Treatof severe thyrotoxicosis should be directed toward the cause of the condition-the overactive thyroid gland, plus the life-threatening sequels of the disease including hyperment
pyrexia, circulatory failure, infection, and, possibly, adrenal insufficiency. Eugene Hospital and Clinic, Eugene Oregon 97401, U.S.A.
BYRON U. MUSA.
PATHOGENESIS OF RETROLENTAL FIBROPLASIA letter SiR,łThe by Dr. Riley and Dr. Slater (Aug. 2, a p. 265) suggesting possible mechanism for the cause of retrolental fibroplasia (R.L.F.) is of considerable interest. Apart from the immediate concern of reducing still further the incidence of this condition in premature babies, the implications are even more widespread in terms of tissue growth and regeneration in general. I agree, however, with the objections raised by Dr. Forrester and Dr. Roberton (Aug. 16), and I doubt the wisdom of putting academic argument into practice at this stage. Unfortunately, Dr. Riley and Dr. Slater seem to be unaware of the extent of the work done at this institute by Prof. Norman Ashton and his colleagues. These studies, reinforced by extensive experimental work in other centres, established oxygen as the primary cause of R.LF., and thus led directly to a considerable control of this disease. Careful investigations spanning more than a decade eliminated many other factors. Indeed, the suggestion that the exposure of immature eyes to light might be a precipitating factor in retrolental fibroplasia is certainly not novel; it was one of the earliest possibilities to be investigated, and with negative results.’ The basis of the pathogenesis of R.L.F. is now known to be the specific destructive effect of oxygen on growing retinal vessels, and this can be produced 1.
Buckle, R. M., Mason,
A. M.
S., Middleton, J. E. Lancet, 1969, i,
1128. 2. 3. 4. 5. 6. 7.
McArthur, J. W., Rawson, R. W., Means, J. H., Cope, O. J. Am. med. Ass. 1947, 34, 868. Waldstein, S. S., Slodki, S. J., Kagniec, G. I., Bronsky, D. Ann. intern. Med. 1960, 52, 626. Lamberg, S. A. Acta med. scand. 1959, 164, 479. Clerkin, E. P., Murphy, R. Med. Clins N. Am. 1966, 50, 569. Baxter, J. D., Bondy, P. K. Ann. intern. Med. 1966, 65, 429. Zacharias, L. Am. J. Ophthal. 1952, 35, 1426.
CONCENTRATIONS SiR,łDr. Shaw (Aug. 9, p. 320) drew attention to the three studies which have compared amine levels in the brainstems of patients who had committed suicide with those in patients who died of other causes. He believes that further studies are indicated since these results suggest a decline in the concentrations of 5-hydroxyindoles in the brainstems of endogenously depressed suicides. However, since no firm conclusions can be drawn from the inconsistent results of these reports, I suggest that we must obtain more information about the many variables affecting amine concentrations, if there is to be any further gain from a repetition of this kind of investigation. If we examine the mean amine levels and standard deviations (s.D.) of the control groups in the previous studies (including that of Maclean et al.1), it can be seen that there is considerable variation in the mean levels of 5-hydroxytryptamine (5-H.T.), and in the individual levels for both 5-H.T. and 5-hydroxyindoleacetic acid (5-H.I.A.A.) in each group.
Figures in parentheses show the number of specimens. Some of the variables which may have contributed to these differences include the terminal illnesses, the age and sex of the patients, any previous drug treatment, the rapidity of death, the time between death and necropsy, the dissection of the specimens, and the methods of assay. All these have been considered in the previous reports, but more detailed studies are needed. Unless the assays are carried out immediately after the
necropsies, another variable is the period of storage while deep-frozen, between necropsy and assay. In addition, even after just a few hours of storage in dry ice, any partial thawing that occurs before homogenisation may also affect the amine levels.5 Dr. Shaw states that the data of Bourne et al.3 are not reliable because of the long periods of storage involved, and because the mean storage time for the controls was longer than that of the suicide group. Since this storage variable is also relevant in the work of Shaw et al.,2 the results of a study in which I investigated the effect of different periods of storage may be of interest. Maclean, R., Nicholson, W. J., Pare, C. M. B., Stacey, R. S. Lancet, 1965, ii, 205. 2. Shaw, D. M., Camps, F. E., Eccleston, E. Br. J. Psychiat. 1967, 113, 1407. 3. Bourne, H. R., Bunney, W. E., Colburn, R. W., Davis, J. M., Davis, J. N., Shaw, D. M., Coppen, A. J. Lancet, 1968, ii, 805. 4. Pare, C. M. B., Yeung, D. P. H., Price, K., Stacey, R. S. Lancet, July 19, 1969, p. 133. 5. Joyce, D. Br. J. Pharmac. Chemother. 1962, 18, 370. 1.
597 A minimum of three brainstem specimens from unwere assayed after storage at -17°C, in sealed plastic bags, for 1, 2, 4, 5, 8, 12, 26, 54, and 75 days after necropsy. After precipitation of protein with zinc sulphate, the 5-H.T. was assayed by the method of Kurtzman et al., modified by the addition of two borate-buffer washes to the ’butanol extract, and the 5-H.I.A.A. was assayed by Ashcroft and Sharman’s method,’ modified by the use of ethyl acetate for the extraction. Internal standards of 5-H.T. and 5-H.I.A.A. were used. The means of the 5-H.T. and 5-H.I.A.A. concentrations were taken after each period of storage, and the following results were obtained: (1) There were significant falls in the mean concentrations of both 5-H.T. (p < 0.01) and 5-H.I.A.A. (p < 0’02) between 1 and 26 days’ storage. Both these falls were of exponential type, levelling off at about 20-25 days. Concentrations after. 54 and 75 days’ storage indicated little subsequent
selected necropsies
change up to 75 days, but longer periods of storage (as cannot
further changes during even in the work of Bourne et al.3)
be ruled out.
(2) On the assumption that the falls were exponential, analysis of all the results gave the following estimated mean
concentrations:
Thus the falls during the first 20-25 days of storage were 34% of the 5-H.T. and 44% of the 5-H.I.A.A. (3) The mean concentrations of the 14 specimens assayed within 5 days of necropsy (mean, 3 days) were: 5-H.T. 550 ng./g., S.D. 93; 5-H.I.A.A. 2830 ng./g., S.D. 948. After allowing for a comparable storage time, the mean concentrations which were found for both 5-H.T. and 5-H.I.A.A. are much higher than those in any of the previous studies. This widens still further the range of mean concentrations which has been found in control groups. The characteristics of the decay process of these amines must depend on such factors as their distribution and routes of degradation, so it is possible that any changes in 5-H.T. metabolism associated with some forms of depressive illness may influence the decay process during storage. It is therefore planned to make a comparison between the decays of a control group and a suicide group, which may indicate changes in amine distribution and routes of degradation which would not necessarily be associated with changes in the amine concentrations. I should like to thank Dr. G. W. Ashcroft for his help and advice. M.R.C. Brain Metabolism Unit, University Medical School, and The Royal Edinburgh Hospital,
Edinburgh.
J. H. DOWSON.
ISCHÆMIC HEART-DISEASE AND THE NEPHROTIC SYNDROME SIR,-Dr. Berlyne and Dr. Mallick (Aug. 23, p. 399) have helped greatly by beginning to collect some facts about the vexed question of ischaemic heart-disease in the nephrotic syndrome. They believe, because of the risk, that " it is essential to use not only steroids but also immunosuppressive agents ". This advice seems debatable, but if it is to be followed it would seem wise to start a prospective registry to record tumours and genetic abnormalities arising in these their progeny, since numbers of young adults will be involved. If this is not done there might be an unusually prolonged " phase of illusion " with immunosuppressive treatment, for the immediate benefits might
patients
or
6.
Kurtzman, R., Shore, P. A., Bogdanksi, D., Brodie, B.
7.
Ashcroft,
J.
Neurochem. 1961, 6, 226. G. W., Sharman, D. F. Br. J. Pharmac. Chemother.
1962, 19, 153.
antecede the disadvantages of the interval.
treatment
Department of Pharmacology and Therapeutics, London Hospital Medical College, E.1.
by
a
long
D. W. VERE.
GENETIC PUNCTUATION SIGNALS SIR,-We should like to comment on Dr. Carter’s third article-" The Genes."1 In discussing the punctuation signals in the genetic code, Dr. Carter mentions the codons UAA, UAG, and UGA as possible signals for beginning and ending polypeptide chains. Studies on Escherichia coli have shown that initiation of protein synthesis is a complex phenomenon involving at least three ribosomal factors, and a particular species of transferR.N.A. (formyl-methionyl-tR.N.A.) which recognises the codon AUG as an initiation signal.2 Many bacteria and bacterial viruses have been shown to utilise this mechanism. Again in E. coli, the codons UAA, UAG, and UGA can serve as signals for chain termination.3 Again special adaptor molecules are involved in the recognition of these codons, in this case proteins, release-factor 1 which recognises UAA and UAG, and release-factor 2 which recognises UAA and UGA.4 5 In higher organisms-especially mammals-there is little information on the mechanisms of initiation and termination. As yet, no patricular adaptor molecules have been shown to play a part in the mechanisms of starting and stopping. Indirect evidence, however, suggests that the termination signals may be the same.67 We hope that future research will provide information on the punctuation mechanisms in mammalian systems, and add to the knowledge of mammalian genetics which Dr. Carter has so thoroughly reviewed. of Biochemical Genetics, National Institutes of Health,
Laboratory
Bethesda, Maryland.
E. M. SCOLNICK C. T. CASKEY.
TELEVISION TEACHING to the teaching of clinical medicinehas been tested in Africa 9 and in American centres.1o In the Uganda trial, using crossover control groups, similar conclusions to those of the Glasgow groups were reached-namely, that television teaching was as efficient as a standard lecture demonstration. In this instance the teaching was presented " live ", with a two-way audio-system, so that it was possible to maintain contact with the audience and therefore achieve a more flexible presentation guided by the reactions of the audience. Videotape recordings and films do not have this flexibility, but can provide a carefully planned demonstration with a full " supporting cast " of visual aids capable of storage for future occasions. This is of particular value in Britain where patients with classical physical signs are not so readily available for teaching sessions. A major advantage of television over lecture-
SiR,ńThe application of television
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Carter, C. O. Lancet, 1969, i, 1087. Iwasaki, K., Sabol, S., Wahba, A. J., Ochoa, S. Archs Biochem. Biophys. 1968, 125, 542., Caskey, C. T., Tompkins, R., Scolnick, E., Caryk, T., Nirenberg, M. Science, N.Y. 1968, 162, 135. Scolnick, E., Tompkins, R., Caskey, T., Nirenberg, M. Proc. natn. Acad. Sci. 1968, 61, 768. Milman, G., Goldstein, J., Scolnick, E., Caskey, T. ibid. (in the press). Caskey, C. T., Beaudet, A., Nirenberg, M. J. Molec. Biol. 1968, 37, 99. Gupta, N. K. J. biol. Chem. 1968, 243, 4959. Kenmure, A. C. F., Thomson, G. O. B., Kennedy, R. D., Cameron, A. J. V. Lancet, Aug. 23, 1969, p. 425. Cantrell, E. G., Craven, J. L. Br. J. med. Educ. 1969, 3, 110. Ramey, J. W. J. med. Educ. 1964, 39, 1107.