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CONVULSANT EFFECT OF PENICILLIN ON THE CEREBRAL CORTEX
115
Assuming that one important mechanism of ageing consists of the gradual accumulation of aberrant cells-with a net loss of chromosomal material and functional capacity--one may expect that a level would ultimately be reached where homoeostatic methanisms could no longer cope with primary and secondary metabolic dysfunctions, a level incompatible with survival. In contrast to unicellular organisms where karyotypic anomalies are subject to natural selection, a complicated multicellular organism may be compared to a civilised community which not only protects its deviant members but may even encourage their propagation. If there is some truth in the old concept that ageing and death are the penalties exacted for differentiation and complex organisation, then all of us would probably be glad to pay the price, given a choice between human frailty and amoebic immortality.
Experimental testing of these theoretical speculations is, of course, highly desirable. The prediction, for example, of an increased variability in chromosome number with age might be subjected to investigation. At the moment, the only chromosome data analysed with respect to age are those of Court Brown. According to his findings, which were interpreted somewhat differently,6 there was a definite tendency toward decline in chromosome number with advancing age. Perhaps some of your readers may be able to furnish data useful in the evaluation of the proposed working hypothesis. Department of Medical Genetics, New York State Psychiatric Institute, Columbia-Presbyterian Medical Center, New York.
LISSY F. JARVIK.
FIFTY YEARS OF RAMSTEDT’S OPERATION
SIR,-Iwas hoping that a surgeon would comment during 1962 that 50 years have now passed since Ramstedt devised his operation for congenital pyloric stenosis. It is doubtful if any operation has saved so many lives and the technique has remained virtually unchanged. The surgical mortality in this condition is now almost nil and this has been brought about in the last 20 years or so by earlier diagnosis and better preoperative managementthe surgery has remained the same. This is a wonderful achievement and babies can nowadays be safely discharged home the day after operation. For an operation to have stood the test of time in this way has won the gratitude of many thousands of children all over the world-this jubilee should not pass unmentioned. Department of Child Health, Llandough Hospital, Penarth, Glamorgan.
A. G. WATKINS.
ELECTROCARDIOGRAPHIC CHANGES ASSOCIATED WITH PHENOTHIAZINE SIR,-We have seen within the past year a number of patients of different ages, transferred to us from other hospitals where they had received treatment with phenothiazine for different periods of time. In approximately 30% we found characteristic features in the E.c.G. which we do not think have been described before. The most striking changes were: low voltage in the standard leads with widening of QRS complexes and flat or isoelectric T especially in AVL and inverted T in the right precordial leads. After treatment was stopped, the E.c.G. returned to normal. No known reason for this pattern, such as myocardial damage, myocarditis, electrolyte dis-
turbances, myxoedema, amyloidosis, pleural effusion, pneumothorax, emphysema, or deformities of thorax, could be found. Malben Hospital,
Shaar-Menashe,
I. TEITELBAUM.
Israel. 6. Court
Brown,
W. M. ibid.
ARTIFICIAL PACING FOR HEART-BLOCK SiR,—The fascinating paper of Dr. Leatham and his colleagues (Dec. 29) raises a small semantic side-issue. As they and others have observed, the electrocardiograms of patients with complete heart-block show a disproportionate frequency of apparent bundle-branch-block patterns. Are these better described as complete heartblock with a ventricular focus below the bifurcation of the bundle ? This postulates one lesion instead of two. St. Helier
Hospital, Carshalton, Surrey.
C. P. PETCH.
POISONOUS PAINTS have SIR,-We recently treated a young child who had eaten some emerald green artist’s water colour which she had squeezed out of a tube. The severity of the vomiting associated with the small amount of colour eaten suggested that the pigment was of high toxicity. Preliminary inquiries from the local art school suggested that the pigment was an arsenical compound of copper, and this was confirmed by analysis. Those of your readers who have to deal with the emergency treatment of poisoning may be interested to know that the manufacturers of artists’ colours issue a caution about the poisonous qualities of the following paints: (a) Cobalt violet (contains arsenate of cobalt). (b) Emerald green (contains aceto-arsenite of copper). (c) Mauve (prepared from an unspecified organic pigment). (d) Purple lake (prepared from synthetic alizarin lakes). The makers issue a booklet of notes on the Composition and Permanence of Artists Colours. This seems to be a further reference book which should be available in every
poisons
centre.
Emergency and Accident Department, Royal Infirmary, Preston.
M. H. HALL.
CONVULSANT EFFECT OF PENICILLIN ON THE CEREBRAL CORTEX SIR,-Ican find no published reference to the con-
vulsant effect of crystalline penicillin when applied to the cerebral cortex. I have inserted this substance after removing bone in open fractures of the skull, sometimes when the dura was torn, without ill effects, and I am therefore prompted to record the following case. An African, aged about 35, was admitted on July 9, 1962, with a swelling over the right parietal bone for 5 months, which had arisen spontaneously without any previous injury. The tumour was round, moderately hard, connected with the skin though not intimately adherent to it, and attached to the underlying bone. There were no localising signs of brain disease. An X-ray of the skull showed a defect in the right parietal bone 11/2 x 11/4 in. with an ill-defined, ragged edge. A leucocyte-count revealed 4300 cells per c.mm. (polymorphs 43%, lymphocytes 51%, and eosinophils 6%). Haemoglobin was 98%. A tentative diagnosis of secondary carcinoma of bone was made. Since the patient complained of severe pain, an operation After was performed under local anxsthesia on July 27. in of a burr-hole was 1 down a made in. scalp, flap turning front of the tumour and enlarged backwards to the edge of the defect through which the growth was protruding from the dura mater. The edge of the body defect was removed round the tumour, and a small incision was made into the dura, through which a probe could easily be passed beneath the tumour. The tumour was removed by snipping through the dura round it and dividing its attachments to the skin. 5,000,000 units of crystalline penicillin was sprinkled into the wound, and the scalp was closed without drainage. On the patient’s return to the ward, unconsciousness set in ’
116 with
severe convulsions, starting in the left arm and becoming generalised. No knee-jerks, ankle-jerks, plantar or abdominal reflexes could be obtained. The temperature was 100.4°F, pulse 168. While the theatre was being prepared for a second operation, phenobarbitone (’Gardenal Sodium’) gr. 6 was injected without effect. A faint, generalised urticarial rash was observed, which had disappeared next morning. Some stitches were removed, the wound was irrigated with saline to remove the penicillin, two rubber-dam drains were inserted, and injections of chlorpheniramine maleate were administered. After consciousness was restored, the drug was continued in tablet form and after irrigation of the wound, there were only five more convulsions. Next morning the patient was fully conscious and feeling well. The report on the growth by Dr. S. T. H. H. Pilbeam stated
that the section showed sheets of reticulin cells with moderate numbers of mitoses and scattered giant-cells indicating a reticulosarcoma. A course of cyclophosphamide (’Endoxan’) 1000 mg. was administered over 5 days, and the patient was discharged on Aug. 21, 1962, with instructions to return for further examination in 1 month. As advised by Hagen1 phenytoin sodium (’ Epanutin ’) and phenobarbitone were supplied for daily use. The patient has not returned for re-examination. I wish to thank the Director of Medical Services for permission to
publish this
case.
Lilongwe Hospitals, Lilongwe, Nyasaland.
S. V. HUMPHRIES.
"
PLANTARIS RUPTURE " SiR,-Ishould like to destroy the myth of the so-called
" plantaris rupture ". This small muscle with a long tendon arises from and is inserted into exactly the same place as the lateral gastrocnemius muscle, which is much larger and stronger. It has always seemed illogical to me that a " small muscle tendon unit " could be ruptured without the larger one being torn as well. Any surgeon who has repaired many ruptures of the tendo Achillis will tell you that the tendon of plantaris is invariably intact and runs across the site of the complete rupture. This letter has been prompted by the experience recently when three patients have reached me more than three months after a typical rupture of the tendo Achillis, because it was thought that they had a " plantaris rupture " and therefore did not need surgery. Tendon-graft surgery in this area is more tedious and less effective than tendon suture. Most myths are attractive and have their origins in some profound universal truth, so let us discard this one, as I am sure it is only the monkey pulling the leg of Homo sapiens. R. C. HOWARD. THE BULGING FONTANELLE
SIR,-In the past few months I have
seen
with bulging of the anterior fontanelle that due to tetracycline.
six infants
was
probably
For various reasons (pharyngitis, tonsillitis, otitis, pyrexia) the infants had received tetracycline compounds in doses of 20-30 mg. per kg. body-weight per 24 hours, for 2 to 3 days. At the time the bulging of the anterior fontanelle was noticed the temperature had come down to normal, and the infants were feeling well and feeding normally. They were not particularly quiet or irritable nor were they vomiting, and besides the sign of the bulging fontanelle there were no abnormal signs. In three infants the fundus oculi was examined, and in two a lumbar puncture was done. All examinations were normal and negative: there were no abnormal reflexes; the normal reflexes were brisk and there were no signs of meningeal 1.
Hagen, D., 1962, Personal communication.
irritation. In all six, the fontanelle returned to normal 2-3 days after stopping the tetracycline. In two cases tetracycline was restarted 6 days after interruption of treatment, and in both bulging of the fontanelle appeared again 24 hours after the reinstitution of tetracycline therapy. Benign intracranial hypertension may occur in infants as a result of administration of tetracycline compounds.1 It seems a pity that intracranial pressure can be measured only by lumbar puncture or by ventricular puncture, thereby exposing the unfortunate infant to (often) unnecessary risk. The tonometer (the instrument for measuring intraocular pressure) could surely be adapted to measure the intracranial pressure in infants. With a broader base, a stronger and longer bolt, and a tougher spring it could be used to measure the tenseness of the protruding fontanelle.
KARL OPFER. THERMOLABILE SERUM FACTOR INFLUENCING THE NEUTRALISATION OF ADENOVIRUS SIR,-In the neutralisation technique of Kjellén et al.,2
diluted 1/2 is tested for its capacity to delay the cytopathic changes induced in HeLa cells by a large dose of adenovirus (in the range of 105-107.5 IDSO per ml. as serum
recorded on the 14th day after inoculation). Usually, sera which after heat inactivation at 56°C for 30 minutes prevent the appearance of such changes for at least 2 days as compared to the virus control are regarded as positive sera. The length of the delay is correlated to the antibody content. By this method, contrary to those in which serum in varying dilutions is tested against a constant virus dose, factors that only in a low dilution of the serum exert an influence on the virus-inhibiting capacity may be revealed even in sera having a high antibody level. By the technique of Kjellen et al. it was found that some sera from healthy children had a greater inhibiting capacity against certain adenovirus types before than after heat inactivation at 56°C for 30 minutes (table I). The serum TABLE I-NEUTRALISATION TESTS WITH SERA FROM HEALTHY CHILDREN
positive both before and after heat inactivation but unheated sample inhibiting more than 2 days longer than the heat-inactivated one.
a =No. of sera
samples had been kept at -30°C for several months. In nearly all cases did the same serum show this effect against only one of the three adenovirus types tested. Sera collected from adolescents and adults known to have had adenovirus type-7 infection 21/2-6 years earlier, were also studied (group 1, table n). These sera had been stored at - 30°C. Unheated and heat-inactivated samples, as well as heat-inactivated samples diluted 1/2 in undiluted fresh guineapig serum instead of in phosphate buffered solution, were tested against adenovirus type 7. Group 2 in table n consists of healthy adults who had not previously been examined by virological methods. The serum samples from these individuals were frozen in sealed ampoules in the dry ice box as soon as possible after collection. There are in the two groups altogether 7 cases in which the serum inhibits adenovirus type 7 more than 2 days longer before than after heat inactivation at 56°C for 30 minutes. By 1. 2.
Fields, J. P. J. Pediat. 1961, 58, 74. Kjellén, L., Sterner, G., Svedmyr, A. Acta paediat., Uppsala, 1957, 46, 164.
Assuming that one important mechanism of ageing consists of the gradual accumulation of aberrant cells-with a net loss of chromosomal material and functional capacity--one may expect that a level would ultimately be reached where homoeostatic methanisms could no longer cope with primary and secondary metabolic dysfunctions, a level incompatible with survival. In contrast to unicellular organisms where karyotypic anomalies are subject to natural selection, a complicated multicellular organism may be compared to a civilised community which not only protects its deviant members but may even encourage their propagation. If there is some truth in the old concept that ageing and death are the penalties exacted for differentiation and complex organisation, then all of us would probably be glad to pay the price, given a choice between human frailty and amoebic immortality.
Experimental testing of these theoretical speculations is, of course, highly desirable. The prediction, for example, of an increased variability in chromosome number with age might be subjected to investigation. At the moment, the only chromosome data analysed with respect to age are those of Court Brown. According to his findings, which were interpreted somewhat differently,6 there was a definite tendency toward decline in chromosome number with advancing age. Perhaps some of your readers may be able to furnish data useful in the evaluation of the proposed working hypothesis. Department of Medical Genetics, New York State Psychiatric Institute, Columbia-Presbyterian Medical Center, New York.
LISSY F. JARVIK.
FIFTY YEARS OF RAMSTEDT’S OPERATION
SIR,-Iwas hoping that a surgeon would comment during 1962 that 50 years have now passed since Ramstedt devised his operation for congenital pyloric stenosis. It is doubtful if any operation has saved so many lives and the technique has remained virtually unchanged. The surgical mortality in this condition is now almost nil and this has been brought about in the last 20 years or so by earlier diagnosis and better preoperative managementthe surgery has remained the same. This is a wonderful achievement and babies can nowadays be safely discharged home the day after operation. For an operation to have stood the test of time in this way has won the gratitude of many thousands of children all over the world-this jubilee should not pass unmentioned. Department of Child Health, Llandough Hospital, Penarth, Glamorgan.
A. G. WATKINS.
ELECTROCARDIOGRAPHIC CHANGES ASSOCIATED WITH PHENOTHIAZINE SIR,-We have seen within the past year a number of patients of different ages, transferred to us from other hospitals where they had received treatment with phenothiazine for different periods of time. In approximately 30% we found characteristic features in the E.c.G. which we do not think have been described before. The most striking changes were: low voltage in the standard leads with widening of QRS complexes and flat or isoelectric T especially in AVL and inverted T in the right precordial leads. After treatment was stopped, the E.c.G. returned to normal. No known reason for this pattern, such as myocardial damage, myocarditis, electrolyte dis-
turbances, myxoedema, amyloidosis, pleural effusion, pneumothorax, emphysema, or deformities of thorax, could be found. Malben Hospital,
Shaar-Menashe,
I. TEITELBAUM.
Israel. 6. Court
Brown,
W. M. ibid.
ARTIFICIAL PACING FOR HEART-BLOCK SiR,—The fascinating paper of Dr. Leatham and his colleagues (Dec. 29) raises a small semantic side-issue. As they and others have observed, the electrocardiograms of patients with complete heart-block show a disproportionate frequency of apparent bundle-branch-block patterns. Are these better described as complete heartblock with a ventricular focus below the bifurcation of the bundle ? This postulates one lesion instead of two. St. Helier
Hospital, Carshalton, Surrey.
C. P. PETCH.
POISONOUS PAINTS have SIR,-We recently treated a young child who had eaten some emerald green artist’s water colour which she had squeezed out of a tube. The severity of the vomiting associated with the small amount of colour eaten suggested that the pigment was of high toxicity. Preliminary inquiries from the local art school suggested that the pigment was an arsenical compound of copper, and this was confirmed by analysis. Those of your readers who have to deal with the emergency treatment of poisoning may be interested to know that the manufacturers of artists’ colours issue a caution about the poisonous qualities of the following paints: (a) Cobalt violet (contains arsenate of cobalt). (b) Emerald green (contains aceto-arsenite of copper). (c) Mauve (prepared from an unspecified organic pigment). (d) Purple lake (prepared from synthetic alizarin lakes). The makers issue a booklet of notes on the Composition and Permanence of Artists Colours. This seems to be a further reference book which should be available in every
poisons
centre.
Emergency and Accident Department, Royal Infirmary, Preston.
M. H. HALL.
CONVULSANT EFFECT OF PENICILLIN ON THE CEREBRAL CORTEX SIR,-Ican find no published reference to the con-
vulsant effect of crystalline penicillin when applied to the cerebral cortex. I have inserted this substance after removing bone in open fractures of the skull, sometimes when the dura was torn, without ill effects, and I am therefore prompted to record the following case. An African, aged about 35, was admitted on July 9, 1962, with a swelling over the right parietal bone for 5 months, which had arisen spontaneously without any previous injury. The tumour was round, moderately hard, connected with the skin though not intimately adherent to it, and attached to the underlying bone. There were no localising signs of brain disease. An X-ray of the skull showed a defect in the right parietal bone 11/2 x 11/4 in. with an ill-defined, ragged edge. A leucocyte-count revealed 4300 cells per c.mm. (polymorphs 43%, lymphocytes 51%, and eosinophils 6%). Haemoglobin was 98%. A tentative diagnosis of secondary carcinoma of bone was made. Since the patient complained of severe pain, an operation After was performed under local anxsthesia on July 27. in of a burr-hole was 1 down a made in. scalp, flap turning front of the tumour and enlarged backwards to the edge of the defect through which the growth was protruding from the dura mater. The edge of the body defect was removed round the tumour, and a small incision was made into the dura, through which a probe could easily be passed beneath the tumour. The tumour was removed by snipping through the dura round it and dividing its attachments to the skin. 5,000,000 units of crystalline penicillin was sprinkled into the wound, and the scalp was closed without drainage. On the patient’s return to the ward, unconsciousness set in ’
116 with
severe convulsions, starting in the left arm and becoming generalised. No knee-jerks, ankle-jerks, plantar or abdominal reflexes could be obtained. The temperature was 100.4°F, pulse 168. While the theatre was being prepared for a second operation, phenobarbitone (’Gardenal Sodium’) gr. 6 was injected without effect. A faint, generalised urticarial rash was observed, which had disappeared next morning. Some stitches were removed, the wound was irrigated with saline to remove the penicillin, two rubber-dam drains were inserted, and injections of chlorpheniramine maleate were administered. After consciousness was restored, the drug was continued in tablet form and after irrigation of the wound, there were only five more convulsions. Next morning the patient was fully conscious and feeling well. The report on the growth by Dr. S. T. H. H. Pilbeam stated
that the section showed sheets of reticulin cells with moderate numbers of mitoses and scattered giant-cells indicating a reticulosarcoma. A course of cyclophosphamide (’Endoxan’) 1000 mg. was administered over 5 days, and the patient was discharged on Aug. 21, 1962, with instructions to return for further examination in 1 month. As advised by Hagen1 phenytoin sodium (’ Epanutin ’) and phenobarbitone were supplied for daily use. The patient has not returned for re-examination. I wish to thank the Director of Medical Services for permission to
publish this
case.
Lilongwe Hospitals, Lilongwe, Nyasaland.
S. V. HUMPHRIES.
"
PLANTARIS RUPTURE " SiR,-Ishould like to destroy the myth of the so-called
" plantaris rupture ". This small muscle with a long tendon arises from and is inserted into exactly the same place as the lateral gastrocnemius muscle, which is much larger and stronger. It has always seemed illogical to me that a " small muscle tendon unit " could be ruptured without the larger one being torn as well. Any surgeon who has repaired many ruptures of the tendo Achillis will tell you that the tendon of plantaris is invariably intact and runs across the site of the complete rupture. This letter has been prompted by the experience recently when three patients have reached me more than three months after a typical rupture of the tendo Achillis, because it was thought that they had a " plantaris rupture " and therefore did not need surgery. Tendon-graft surgery in this area is more tedious and less effective than tendon suture. Most myths are attractive and have their origins in some profound universal truth, so let us discard this one, as I am sure it is only the monkey pulling the leg of Homo sapiens. R. C. HOWARD. THE BULGING FONTANELLE
SIR,-In the past few months I have
seen
with bulging of the anterior fontanelle that due to tetracycline.
six infants
was
probably
For various reasons (pharyngitis, tonsillitis, otitis, pyrexia) the infants had received tetracycline compounds in doses of 20-30 mg. per kg. body-weight per 24 hours, for 2 to 3 days. At the time the bulging of the anterior fontanelle was noticed the temperature had come down to normal, and the infants were feeling well and feeding normally. They were not particularly quiet or irritable nor were they vomiting, and besides the sign of the bulging fontanelle there were no abnormal signs. In three infants the fundus oculi was examined, and in two a lumbar puncture was done. All examinations were normal and negative: there were no abnormal reflexes; the normal reflexes were brisk and there were no signs of meningeal 1.
Hagen, D., 1962, Personal communication.
irritation. In all six, the fontanelle returned to normal 2-3 days after stopping the tetracycline. In two cases tetracycline was restarted 6 days after interruption of treatment, and in both bulging of the fontanelle appeared again 24 hours after the reinstitution of tetracycline therapy. Benign intracranial hypertension may occur in infants as a result of administration of tetracycline compounds.1 It seems a pity that intracranial pressure can be measured only by lumbar puncture or by ventricular puncture, thereby exposing the unfortunate infant to (often) unnecessary risk. The tonometer (the instrument for measuring intraocular pressure) could surely be adapted to measure the intracranial pressure in infants. With a broader base, a stronger and longer bolt, and a tougher spring it could be used to measure the tenseness of the protruding fontanelle.
KARL OPFER. THERMOLABILE SERUM FACTOR INFLUENCING THE NEUTRALISATION OF ADENOVIRUS SIR,-In the neutralisation technique of Kjellén et al.,2
diluted 1/2 is tested for its capacity to delay the cytopathic changes induced in HeLa cells by a large dose of adenovirus (in the range of 105-107.5 IDSO per ml. as serum
recorded on the 14th day after inoculation). Usually, sera which after heat inactivation at 56°C for 30 minutes prevent the appearance of such changes for at least 2 days as compared to the virus control are regarded as positive sera. The length of the delay is correlated to the antibody content. By this method, contrary to those in which serum in varying dilutions is tested against a constant virus dose, factors that only in a low dilution of the serum exert an influence on the virus-inhibiting capacity may be revealed even in sera having a high antibody level. By the technique of Kjellen et al. it was found that some sera from healthy children had a greater inhibiting capacity against certain adenovirus types before than after heat inactivation at 56°C for 30 minutes (table I). The serum TABLE I-NEUTRALISATION TESTS WITH SERA FROM HEALTHY CHILDREN
positive both before and after heat inactivation but unheated sample inhibiting more than 2 days longer than the heat-inactivated one.
a =No. of sera
samples had been kept at -30°C for several months. In nearly all cases did the same serum show this effect against only one of the three adenovirus types tested. Sera collected from adolescents and adults known to have had adenovirus type-7 infection 21/2-6 years earlier, were also studied (group 1, table n). These sera had been stored at - 30°C. Unheated and heat-inactivated samples, as well as heat-inactivated samples diluted 1/2 in undiluted fresh guineapig serum instead of in phosphate buffered solution, were tested against adenovirus type 7. Group 2 in table n consists of healthy adults who had not previously been examined by virological methods. The serum samples from these individuals were frozen in sealed ampoules in the dry ice box as soon as possible after collection. There are in the two groups altogether 7 cases in which the serum inhibits adenovirus type 7 more than 2 days longer before than after heat inactivation at 56°C for 30 minutes. By 1. 2.
Fields, J. P. J. Pediat. 1961, 58, 74. Kjellén, L., Sterner, G., Svedmyr, A. Acta paediat., Uppsala, 1957, 46, 164.