- Email: [email protected]
SEIZURES IN PSYCHOTIC CHILDREN
47
hasmopoietic tissues, were modified in structure and assumed forms similar, in some ultrastructural aspects, to normal medullary cells.7 De Carvalhohas shown that, by injecting into the medullary cavity of leukasmic patients R.N.A. obtained from haemopoietic cells of normal subjects, the leuksemic picture is improved locally. We have confirmed this,9 using R.N.A. obtained from hxmopoietic cells of animals. On the basis of these results we treated two patients with myeloid chronic leukaemia with large doses of R.N.A. obtained from hsemopoietic animal cells. The R.N.A. was obtained by the method previously described.9 200 mg. of 100 mg. R.N.A. a day was administered intravenously. was injected in 10 minutes, and the remaining 100 mg. immediately afterwards by means of slow infusion over a period of 2 hours. This was done in order to maintain a high blood concentration of the substance for as long as possible. This treatment was continued for 15 days. The behaviour of the white cells in the peripheral blood was as
the myelopoiesis in the bone-marrow. In that event a reduction in the total number of white blood-cells would be observed. We cannot yet state whether, in leukaemic patients, R.N.A. causes normalisation of the myelopoiesis or only stimulates cell maturation. This will only be revealed by prolonged further study of the patients under treatment.
S. P. B. L.
Medical Clinic, University of Pavia, Italy.
ESPOSITO FORNAROLI CASTELLI BUSCARINI.
A GENETIC THEORY OF INFLAMMATORY POLYARTHRITIS
follows: Case 1.-Before treatment: 64,500 per c.mm. (promyelocytes 10%, myelocytes 34%, metamyelocytes 14%, young mature granulocytes 27%, lymphocytes 8%, After treatment: 65,200 per c.mm. (myelo-
granulocytes 5%, monocytes 2%). cytes 10%, metamyelocytes 9%, young granulocytes 36%, mature granulocytes 40%, lymphocytes 4%, monocytes 1%). Case 2.-Before treatment: 71,000 per c.mm. (promyelocytes 24%, myelocytes 30%, metamyelocytes 16%, young granulocytes 4%, mature granulocytes 19%, lymphocytes 6%, monocytes 1%). After treatment: 62,500 per c.mm. (myelocytes 11%, metamyelocytes 15%, young granulocytes 29%, mature granulocytes 39%, lymphocytes 5%, monocytes 1%).
In neither of the cases were significant modifications of the erythrocytes, reticulocytes, or platelets, registered. The behaviour of the granuloblastic cells of the bonemarrow is summarised in the accompanying table. PROPORTION OF GRANULOBLASTIC CELLS IN 2 PATIENTS WITH CHRONIC MYELOID LEUKAMIA BEFORE AND AFTER TREATMENT WITH R.N.A.
(%)
Immunochemistry Unit for Cancer Research, Department of Bacteriology, University of Liverpool.
R. AUGUSTIN.
Department of Theoretical
Physics,
Clarendon Laboratory, Oxford.
J. A. SPIERS.
SHINGLES RECONSIDERED
SIR,—Your interesting reviewof Dr. R. E. HopeSimpson’s Albert Wander lecture prompts me to record that about ten years ago a young man of my acquaintance developed typical shingles on the trunk. Within a day or two a footballer friend of his two lads shared a football
had the
trouble. These changing-room and shower facilities with a third friend who had developed shingles about a fortnight previously. None of the team had chickenpox at that time, but they all thought they had had it in childhood. same
Public Health Laboratory, Town Hall, Edmonton, London, N.9.
MAIR THOMAS.
SEIZURES IN PSYCHOTIC CHILDREN
These results show that the
R.N.A.
obtained from
hxmopoietic animal cells stimulates the maturation of leukaemic cells, when administered intravenously in large doses. The appearance of a high percentage of mature cells both in the bone-marrow and in the peripheral blood is not, however, accompanied by a corresponding drop in the total number of white blood-cells. We believe that this phenomenon is due to the fact that in leuksemic patients the R.N.A. acts on a vast territory of myeloid tissue. All the cells of this tissue are stimulated maturation but are not reduced in number. This agrees with present notions about the action on cells of exogenous R.N.A.: this substance in fact acts on cytodifferentiation and not as an antimitotic or cytolytic drug. Theoretically, if the R.N.A. had caused" normalisation " of the leukaemic cells, the extramedullary myelopoiesis function should, as a result, diminish on account of those mechanisms which, in a normal subject, localise
to
7. Esposito, S. Experientia, 1964, 20, 69. 8. De Carvalho, S. Nature, Lond. 1963, 197, 1077. 9. Esposito, S., Fornaroli, P., Buscarini, L., Castelli, B.
(in the press).
Hœmatologica
SIR,-Dr. Boardman’simputations are interesting, and if proved generally acceptable may occasion some critical reappraisal of current psychiatric diagnosis. His contention that " some psychotic children and adults with , convulsive ’ E.E.G.S form a separate group " merits inquiry along the following lines: 1. What are the characteristic distinguishing psychiatric features of this group which are often found ? 2. What significant minor neurological abnormalities may
they display ? 3. Does the
upon clinical or the latter, in what this group is there
diagnosis depend mainly both ? With respect
findings proportion of patients designated E.E.G.
or
to
to
correlation between the two ? 4. What is the estimated incidence of this " separate group " of adults encountered in ordinary mental hospitals and outpatient psychiatric practice ? 5. What is the possible aetiology of the condition ? I have often wondered how much importance should be attached to E.E.G. findings alone, and I would be most interested to ascertain whether Dr. Boardman or others have observed 1. Lancet, 1964, i, 1391. 2. ibid. p. 1280. 3. ibid. p. 1376. 4. Boardman, R. H. ibid.
p. 1443.
48 much regional variation in the type of reports which emanate from different E.E.G. centres. Whilst working at one mental hospital I was impressed by the large number of E.E.G.S which were reported to be abnormal, whereas subsequent experience derived from patients at this hospital has intimated trends in the reverse direction. Perhaps Dr. Boardman may have overcome this discrepancy by interpretation of his E.E.G. records according to some special criteria. Should his group prove to be a significant one, however, important practical implications arise with regard to treatment; for instance, should anticonvulsants be substituted for or prescribed in conjunction with phenothiazines in these patients, some of whom might otherwise be regarded as schizophrenics ? We should, perhaps, examine the diagnosis more carefully when presented with an apparently psychotic individual, but as a possible first step towards elucidation of this complex problem, I would, with respect, question the necessity or justification for performing E.E.G.s on large numbers of our
psychotic patients. Shelton Hospital, Shrewsbury, Shropshire
J. C. BARKER.
HIGHER
QUALIFICATIONS SIR,-Examinations are, or should be, of
two
main
kinds, those which test knowledge, and those which test originality and reasoning power. Into the first group fall those which establish (a) minimum knowledge for the practice of the profession or of a specialty within it, or (b) a more advanced level of knowledge. A certain measure of application is needed for these, but, given adequate application (different in extent for each individual), limitation of intellect should rarely, and probably rarely does, prevent ultimate success. Learning demands little intellect. Only ability to unlearn in the face of reason truly tests mental capacity. The second group also requires evidence of knowledge, though often wider in a narrower field; but in addition it should demand good evidence of intellectual ability, originality, and reasoning power. In this group a thesis is always called for, and should be strictly judged for such evidence. If ever such categories could be recognised, it would be up to the universities and colleges, and their examiners, to codify their various degrees and make them as far as possible equivalent.
Unless some such manoeuvre is present jungle of British medical
become impenetrable. London, W.1.
adopted, the degrees may soon soon
H. DAINTREE JOHNSON.
MEBANAZINE
SIR,-Ihave read with interest the article by Dr. Cooper and Dr. Keddie (May 23). I have now been using mebanazine (’Actomol’) for over a year, and have treated a total of 72 inpatients and outpatients with it. I have used only 15 mg. per day as a routine, and
failure to respond to this dose has caused me to discontinue the drug, though in 2 cases only, where response was partial, the dose was increased to 20 mg. a day. The only side-effects which I have observed have been excessive drowsiness, necessitating withdrawal of the drug, in 2 patients; transient postural hypotension, which wore off spontaneously in a few days, in 6 patients; and complaints of
impotence by
2
men.
I venture to suggest that the rigid dosage regimen used by the authors was unwise, and had they selected as a dose that recommended by the manufacturers-i.e., 15-20 mg. per day -they would not have experienced the dramatic consequences that they did. I have found mebanazine an effective and safe drug in the treatment of atypical depression as described by Sargant,l with a success-rate certainly as high as with other 1.
Sargant, W. Brit. med. J. 1961, i, 225.
M.A.O.I.S, and generally less disturbing for the patient to take. I think it would be a pity to damn such a useful drug on the basis of 3 adverse reactions to excessive dosage. Storthes Hall Hospital, C. F. HERRIDGE. Kirkburton, Yorks.
CHELATING AGENTS IN GAS-GANGRENE SIR,-In 1956 I demonstrated that it was possible to protect against the lethal effects of Clostridium perfringens type-A toxin with a metal-chelating compound,l and that this compound-calcium edetate (calcium E.D.T.A.,
’Versenate’)-was also useful in protecting animals against experimental gas-gangrened2 Subsequent publicationsfurther elucidated the mode of action of this compound. These results indicate that calcium edetate should be of value as a therapeutic agent in treating gas-gangrene either by systemic administration or by topical application to the wound. This work has been confirmed by other workers.4 Calcium edetate is non-toxic when given systemically and is an accepted drug for the treatment of lead-poisoning in children. I have not seen any reports of the use or attempted use of calcium edetate for the treatment of gasgangrene, and wish to call attention to the potential usefulness of this compound. In current experiments we have found that another chelating agent whose pharmacological properties are also known-diethylenetriaminepentaacetic acid (D.T.P.A.)-is almost ten times as effective as calcium edetate when utilised in the manner described in the publications cited above. Department
of
Biological Sciences,
Purdue University, Lafayette, Indiana 47907, U.S.A.
MERWIN MOSKOWITZ.
HERMAPHRODITISM
SIR,-Having been interested in hermaphroditism for years, I have followed the various noteworthy articles on the subject in The Lancet with particular attention, in order to examine new knowledge with reference to the theory proposed by me in 1938 that hermaphroditism, defined as genital-tract heterosexuality, is foetal hypogonadism in males and foetal masculinisation some
in females. Male fcetal hypogonads (male external
hermaphrodites) have
genitalia because during the period of urogenital-sinus development there was not sufficient testis hormonal activity to stimulate the formation of a penis and scrotum. These individuals have been found to have a normal male chromosomal design (XY). This should be decisive in identifying their sex as male. Despite this, most writers assert that these individuals are female. To maintain this view it is necessary to misinterpret the XY chromosomal design as an abnormal female one, and to mistake such signs of hypogonadism as beardlessness and gynascomastia for femaleness. In females, testicular foetal masculinisation is due to the factor responsible for the occurrence of testicular tumours of the ovary in later life-i.e., the ovary does not always develop free of testis cells. When such cells become active early in foetal development one or both ovaries may become partially or completely supplanted by an anomalous testis, just as in later life one or both ovaries may become partially or completely replaced by arrhenoblastomas. Females with complete supplantation of the ovaries by anomalous testes (male internal hermaphrodites) have been found to have an abnormal female chromosomal design (XO). Females with partial supplantation of the ovary by an anoma-
labial external
1. Science, 1956, 123, 1077. 2. Proc. Soc. exp. Biol., N.Y. 1956, 92, 706. 3. Nature, Lond. 1958, 181, 550; and in Metal Binding in Medicine (edited by M. J. Seven). Philadelphia, 1960. 4. Bittner, J., Voinesco, V., Winter, D. Arch. roum. Path. exp. 1959, 18, 467; ibid. 1961, 20, 717.
hasmopoietic tissues, were modified in structure and assumed forms similar, in some ultrastructural aspects, to normal medullary cells.7 De Carvalhohas shown that, by injecting into the medullary cavity of leukasmic patients R.N.A. obtained from haemopoietic cells of normal subjects, the leuksemic picture is improved locally. We have confirmed this,9 using R.N.A. obtained from hxmopoietic cells of animals. On the basis of these results we treated two patients with myeloid chronic leukaemia with large doses of R.N.A. obtained from hsemopoietic animal cells. The R.N.A. was obtained by the method previously described.9 200 mg. of 100 mg. R.N.A. a day was administered intravenously. was injected in 10 minutes, and the remaining 100 mg. immediately afterwards by means of slow infusion over a period of 2 hours. This was done in order to maintain a high blood concentration of the substance for as long as possible. This treatment was continued for 15 days. The behaviour of the white cells in the peripheral blood was as
the myelopoiesis in the bone-marrow. In that event a reduction in the total number of white blood-cells would be observed. We cannot yet state whether, in leukaemic patients, R.N.A. causes normalisation of the myelopoiesis or only stimulates cell maturation. This will only be revealed by prolonged further study of the patients under treatment.
S. P. B. L.
Medical Clinic, University of Pavia, Italy.
ESPOSITO FORNAROLI CASTELLI BUSCARINI.
A GENETIC THEORY OF INFLAMMATORY POLYARTHRITIS
follows: Case 1.-Before treatment: 64,500 per c.mm. (promyelocytes 10%, myelocytes 34%, metamyelocytes 14%, young mature granulocytes 27%, lymphocytes 8%, After treatment: 65,200 per c.mm. (myelo-
granulocytes 5%, monocytes 2%). cytes 10%, metamyelocytes 9%, young granulocytes 36%, mature granulocytes 40%, lymphocytes 4%, monocytes 1%). Case 2.-Before treatment: 71,000 per c.mm. (promyelocytes 24%, myelocytes 30%, metamyelocytes 16%, young granulocytes 4%, mature granulocytes 19%, lymphocytes 6%, monocytes 1%). After treatment: 62,500 per c.mm. (myelocytes 11%, metamyelocytes 15%, young granulocytes 29%, mature granulocytes 39%, lymphocytes 5%, monocytes 1%).
In neither of the cases were significant modifications of the erythrocytes, reticulocytes, or platelets, registered. The behaviour of the granuloblastic cells of the bonemarrow is summarised in the accompanying table. PROPORTION OF GRANULOBLASTIC CELLS IN 2 PATIENTS WITH CHRONIC MYELOID LEUKAMIA BEFORE AND AFTER TREATMENT WITH R.N.A.
(%)
Immunochemistry Unit for Cancer Research, Department of Bacteriology, University of Liverpool.
R. AUGUSTIN.
Department of Theoretical
Physics,
Clarendon Laboratory, Oxford.
J. A. SPIERS.
SHINGLES RECONSIDERED
SIR,—Your interesting reviewof Dr. R. E. HopeSimpson’s Albert Wander lecture prompts me to record that about ten years ago a young man of my acquaintance developed typical shingles on the trunk. Within a day or two a footballer friend of his two lads shared a football
had the
trouble. These changing-room and shower facilities with a third friend who had developed shingles about a fortnight previously. None of the team had chickenpox at that time, but they all thought they had had it in childhood. same
Public Health Laboratory, Town Hall, Edmonton, London, N.9.
MAIR THOMAS.
SEIZURES IN PSYCHOTIC CHILDREN
These results show that the
R.N.A.
obtained from
hxmopoietic animal cells stimulates the maturation of leukaemic cells, when administered intravenously in large doses. The appearance of a high percentage of mature cells both in the bone-marrow and in the peripheral blood is not, however, accompanied by a corresponding drop in the total number of white blood-cells. We believe that this phenomenon is due to the fact that in leuksemic patients the R.N.A. acts on a vast territory of myeloid tissue. All the cells of this tissue are stimulated maturation but are not reduced in number. This agrees with present notions about the action on cells of exogenous R.N.A.: this substance in fact acts on cytodifferentiation and not as an antimitotic or cytolytic drug. Theoretically, if the R.N.A. had caused" normalisation " of the leukaemic cells, the extramedullary myelopoiesis function should, as a result, diminish on account of those mechanisms which, in a normal subject, localise
to
7. Esposito, S. Experientia, 1964, 20, 69. 8. De Carvalho, S. Nature, Lond. 1963, 197, 1077. 9. Esposito, S., Fornaroli, P., Buscarini, L., Castelli, B.
(in the press).
Hœmatologica
SIR,-Dr. Boardman’simputations are interesting, and if proved generally acceptable may occasion some critical reappraisal of current psychiatric diagnosis. His contention that " some psychotic children and adults with , convulsive ’ E.E.G.S form a separate group " merits inquiry along the following lines: 1. What are the characteristic distinguishing psychiatric features of this group which are often found ? 2. What significant minor neurological abnormalities may
they display ? 3. Does the
upon clinical or the latter, in what this group is there
diagnosis depend mainly both ? With respect
findings proportion of patients designated E.E.G.
or
to
to
correlation between the two ? 4. What is the estimated incidence of this " separate group " of adults encountered in ordinary mental hospitals and outpatient psychiatric practice ? 5. What is the possible aetiology of the condition ? I have often wondered how much importance should be attached to E.E.G. findings alone, and I would be most interested to ascertain whether Dr. Boardman or others have observed 1. Lancet, 1964, i, 1391. 2. ibid. p. 1280. 3. ibid. p. 1376. 4. Boardman, R. H. ibid.
p. 1443.
48 much regional variation in the type of reports which emanate from different E.E.G. centres. Whilst working at one mental hospital I was impressed by the large number of E.E.G.S which were reported to be abnormal, whereas subsequent experience derived from patients at this hospital has intimated trends in the reverse direction. Perhaps Dr. Boardman may have overcome this discrepancy by interpretation of his E.E.G. records according to some special criteria. Should his group prove to be a significant one, however, important practical implications arise with regard to treatment; for instance, should anticonvulsants be substituted for or prescribed in conjunction with phenothiazines in these patients, some of whom might otherwise be regarded as schizophrenics ? We should, perhaps, examine the diagnosis more carefully when presented with an apparently psychotic individual, but as a possible first step towards elucidation of this complex problem, I would, with respect, question the necessity or justification for performing E.E.G.s on large numbers of our
psychotic patients. Shelton Hospital, Shrewsbury, Shropshire
J. C. BARKER.
HIGHER
QUALIFICATIONS SIR,-Examinations are, or should be, of
two
main
kinds, those which test knowledge, and those which test originality and reasoning power. Into the first group fall those which establish (a) minimum knowledge for the practice of the profession or of a specialty within it, or (b) a more advanced level of knowledge. A certain measure of application is needed for these, but, given adequate application (different in extent for each individual), limitation of intellect should rarely, and probably rarely does, prevent ultimate success. Learning demands little intellect. Only ability to unlearn in the face of reason truly tests mental capacity. The second group also requires evidence of knowledge, though often wider in a narrower field; but in addition it should demand good evidence of intellectual ability, originality, and reasoning power. In this group a thesis is always called for, and should be strictly judged for such evidence. If ever such categories could be recognised, it would be up to the universities and colleges, and their examiners, to codify their various degrees and make them as far as possible equivalent.
Unless some such manoeuvre is present jungle of British medical
become impenetrable. London, W.1.
adopted, the degrees may soon soon
H. DAINTREE JOHNSON.
MEBANAZINE
SIR,-Ihave read with interest the article by Dr. Cooper and Dr. Keddie (May 23). I have now been using mebanazine (’Actomol’) for over a year, and have treated a total of 72 inpatients and outpatients with it. I have used only 15 mg. per day as a routine, and
failure to respond to this dose has caused me to discontinue the drug, though in 2 cases only, where response was partial, the dose was increased to 20 mg. a day. The only side-effects which I have observed have been excessive drowsiness, necessitating withdrawal of the drug, in 2 patients; transient postural hypotension, which wore off spontaneously in a few days, in 6 patients; and complaints of
impotence by
2
men.
I venture to suggest that the rigid dosage regimen used by the authors was unwise, and had they selected as a dose that recommended by the manufacturers-i.e., 15-20 mg. per day -they would not have experienced the dramatic consequences that they did. I have found mebanazine an effective and safe drug in the treatment of atypical depression as described by Sargant,l with a success-rate certainly as high as with other 1.
Sargant, W. Brit. med. J. 1961, i, 225.
M.A.O.I.S, and generally less disturbing for the patient to take. I think it would be a pity to damn such a useful drug on the basis of 3 adverse reactions to excessive dosage. Storthes Hall Hospital, C. F. HERRIDGE. Kirkburton, Yorks.
CHELATING AGENTS IN GAS-GANGRENE SIR,-In 1956 I demonstrated that it was possible to protect against the lethal effects of Clostridium perfringens type-A toxin with a metal-chelating compound,l and that this compound-calcium edetate (calcium E.D.T.A.,
’Versenate’)-was also useful in protecting animals against experimental gas-gangrened2 Subsequent publicationsfurther elucidated the mode of action of this compound. These results indicate that calcium edetate should be of value as a therapeutic agent in treating gas-gangrene either by systemic administration or by topical application to the wound. This work has been confirmed by other workers.4 Calcium edetate is non-toxic when given systemically and is an accepted drug for the treatment of lead-poisoning in children. I have not seen any reports of the use or attempted use of calcium edetate for the treatment of gasgangrene, and wish to call attention to the potential usefulness of this compound. In current experiments we have found that another chelating agent whose pharmacological properties are also known-diethylenetriaminepentaacetic acid (D.T.P.A.)-is almost ten times as effective as calcium edetate when utilised in the manner described in the publications cited above. Department
of
Biological Sciences,
Purdue University, Lafayette, Indiana 47907, U.S.A.
MERWIN MOSKOWITZ.
HERMAPHRODITISM
SIR,-Having been interested in hermaphroditism for years, I have followed the various noteworthy articles on the subject in The Lancet with particular attention, in order to examine new knowledge with reference to the theory proposed by me in 1938 that hermaphroditism, defined as genital-tract heterosexuality, is foetal hypogonadism in males and foetal masculinisation some
in females. Male fcetal hypogonads (male external
hermaphrodites) have
genitalia because during the period of urogenital-sinus development there was not sufficient testis hormonal activity to stimulate the formation of a penis and scrotum. These individuals have been found to have a normal male chromosomal design (XY). This should be decisive in identifying their sex as male. Despite this, most writers assert that these individuals are female. To maintain this view it is necessary to misinterpret the XY chromosomal design as an abnormal female one, and to mistake such signs of hypogonadism as beardlessness and gynascomastia for femaleness. In females, testicular foetal masculinisation is due to the factor responsible for the occurrence of testicular tumours of the ovary in later life-i.e., the ovary does not always develop free of testis cells. When such cells become active early in foetal development one or both ovaries may become partially or completely supplanted by an anomalous testis, just as in later life one or both ovaries may become partially or completely replaced by arrhenoblastomas. Females with complete supplantation of the ovaries by anomalous testes (male internal hermaphrodites) have been found to have an abnormal female chromosomal design (XO). Females with partial supplantation of the ovary by an anoma-
labial external
1. Science, 1956, 123, 1077. 2. Proc. Soc. exp. Biol., N.Y. 1956, 92, 706. 3. Nature, Lond. 1958, 181, 550; and in Metal Binding in Medicine (edited by M. J. Seven). Philadelphia, 1960. 4. Bittner, J., Voinesco, V., Winter, D. Arch. roum. Path. exp. 1959, 18, 467; ibid. 1961, 20, 717.