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IgA AND PRIMARY AMŒBIC MENINGOENCEPHALITIS
441 have alleviated suffering in the specific instance of British antilewisite. This was very effective against lewisite in the rabbit’s eye and would probably have been in man also. Pedler: "Do you agree with me that that experiment was within the meaning of the Act illegal?" The work was ordered by the Ministry of Supply. It presumably has the same legality as war. Pedler: "I too am a responsible scientist and have given you an accurate account of the paper". Readers must judge for themselves whether Pedler has shown scientific responsibility in his account of the research. One can understand why he did not wish to reveal his sources. alike, must have been disMany people, doctors and tressed by the implication that the work was done almost mindlessly with no preventive or curative aim. Doctors will not need reminding that B.A.L. (dimercaprol) is still in use and that mustard-gas derivatives are important in the treatment of some forms of cancer.
laymen
Department of Physiology, London Hospital Medical College,
K. W. CROSS
London E1 2AD
DIAGNOSIS OF LEGIONNAIRES’ DISEASE
SIR,-Dr Plotkin (Feb. 3,
p. 271), referring to our report on of legionnaires’ disease with severe cerebral disturbance,l states that in the absence of cultural confirmation he does not regardthe diagnosis as having been established: this would apply to all but a few reported cases of legionnaires’ disease in which patients have survived the illness, since culture of the organism from sputum or respiratory secretions has so far rarely been successful. Plotkin warns us (unnecessarily) of the difficulty of making a diagnosis solely on the basis of serological tests: the diagnosis was in fact based not only on rising titres to legionnaires’ disease antigen but also on clinical features suggestive of legionnaires’ disease and on the exclusion, as far as possible, of other causes of the illness. Plotkin states: "The diagnosis in the second reported patient was based initially on clinical response to erythromycin: such reasoning is untenable." The diagnosis, in fact, rested initially on clinical features suggestive of legionnaires’ disease and particularly on the neurological disturbance which resembled that in a case previously encountered. A case of legionnaires’ disease with dysarthria and ataxia has been reported2 and another case with dysarthria and ataxia persisting long after the acute illness has been seen at Belvidere Hospital, Glasgow (W. C. Love, personal communication). We suggest it would be worthwhile to give erythromycin tc patients with the clinical features we describe pending the results of serological studies and culture of respiratory secretwo cases
tions.
A. W. LEES W. F. TYRRELL
Ruchill Hospital, Glasgow
IgA AND PRIMARY AMŒBIC MENINGOENCEPHALITIS
StR,-Last July a girl of 11 died from primary amoebic meningoencephalitis due to Naegleria fowleri, which developed within 5 days of swimming in a heated indoor pool supplied with water from hot springs. These were later shown to be infected by N. fowleri. Stimulated by the report drom Dr Cursons and colleagues (Jan. 27, p. 233) of low IgA levels in a case of primary amoebic meningoencephalitis similarly related to
bathing, the third
we
have examined serum taken from our patient on of disease and find the immunoglobulins are
day
1 Lees, A W., Tyrrell, W. F. Lancet, 1978, ii, 1336. 2 Gasper, T. M, Farndon, P. A, Davies, R. Br. med. J. 1978, ii, 1611.
within normal limits. The values (normal limits in parentheses) in g/1 were: IgA 1-5(0.9.$), IgG 10 -(8.0-18.0), IgM 1.9 (0.6-2.8). The same serum showed no reaction at a dilution of 1/8 in a fluorescent antibody test against N. fowleri. A full account of this case will be published elsewhere. We thank the department of chemical pathology, University College Hospital, London, for the immunoglobulin estimations.
Royal
United
Hospital,
A. R. R. CAIN
Bath
Public Health Laboratory, Royal United Hospital (North), Bath BA1 3NG
P. G. MANN
Amœbiasis Reference Unit,
Department of Pathology, Hospital for Tropical Diseases,
D. C. WARHURST
London NW1
ABSENCE OF ANTI-ACETYLCHOLINE RECEPTOR ANTIBODIES IN CONGENITAL MYASTHENIA GRAVIS
SIR,-In about 1’c, of patients with myasthenia gravis (M.G.) symptoms and signs are present at birth or are evident shortly after. This congenital form of M.G. differs from "acquired" M.G. of later onset in that males are predominantly affected and the familial incidence is high. Although thymic changes have been reported in the congenital cases, there is no clear evidence that thymectomy or other immunosuppressive treatment is useful. The disease is generally non-progressive. Congenital M.G. needs to be distinguished from familial infantile M.G. in which severe respiratory and feeding difficulties are common, particularly during the neonatal period or during infection. In familial infantile M.G. spontaneous remission can occur.I There is now good evidence that acquired M.G. is an autoimmune disease and that anti-acetylcholine receptor (AChR) antibodies are implicated in causing the disorder of neuromuscular transmission. This antibody is present in over 83% of patients when detected by an immunoprecipitation assay with ’1-bungarotoxin (a-BuTx) labelled extracts of human muscle.2.3 The proportion of patients in whom the antibody is detectable by this assay is smaller in those with pure ocular M.G. (75%) than in those with generalised weakness (>9S%). M.G. sera can also inhibit the binding of x-BuTx to human AChR.3 M.G. immunoglobulin can passively transfer the disease to mice4 and plasma exchange causes a short-lived clinical remission in most patients associated with a temporary reduction in anti-AChR levels.5 In neonatal M.G., a transient illness mothers, occurring in about 12% of babies born to myasthenic maternal anti-AChR antibodies are present.6 We have measured antibodies in six patients with congenital M.G. aged between 6 and 25, all of whom were males. Two of the patients were brothers, and two were the sons of a cousin marriage. Symptoms began at birth or, in the case of one of the brothers, at 18 months. All but one had marked extraocular weakness and all had mild to severe generalised weakness at the time of study. Electromyographic studies in four patients showed evidence of a neuromuscular transmission defect. The response to ’Tensilon’ (edrophonium) was positive, and anticholinesterase treatment was beneficial in all cases. Anti-AChR antibodies, as determined by the immunoprecipitation assay using human AChR, were not detected in any of the six cases. Mean antibody titres were 0-05+0-1nmol/1 (mean + s.D. of three separate determinations on each patient) 1. Fenichel, G. M Archs Neurol 1978, 35, 97. 2. Lindstrom, J. M, Scybold, M E., Lennon, V. A., Whittingham, S., Duane, D. D. Neurology, 1976, 26, 1054 3. Vincent, A., Newsom-Davis, J. in Neurotoxins Tools in neurobiology edited be F. Clementi and F. Ceccarelli) New York in the press. 4. Toyka, E V, Drachman, D B, Griffin, D E, Pestronk, A, Winkelstein, J A., Fischbeck, K H., Kao, I. New Engl J Med, 1977, 296, 125 5. Newsom-Davis, J, Pinching, A. J., Vincent, A, Wilson, S G Neurology, 6.
1978, 28, 266. Keesey, J., Lindstrom, J. M., Cokely,
H New
Engl. J
Med 1977,
296, 55.
laymen
Department of Physiology, London Hospital Medical College,
K. W. CROSS
London E1 2AD
DIAGNOSIS OF LEGIONNAIRES’ DISEASE
SIR,-Dr Plotkin (Feb. 3,
p. 271), referring to our report on of legionnaires’ disease with severe cerebral disturbance,l states that in the absence of cultural confirmation he does not regardthe diagnosis as having been established: this would apply to all but a few reported cases of legionnaires’ disease in which patients have survived the illness, since culture of the organism from sputum or respiratory secretions has so far rarely been successful. Plotkin warns us (unnecessarily) of the difficulty of making a diagnosis solely on the basis of serological tests: the diagnosis was in fact based not only on rising titres to legionnaires’ disease antigen but also on clinical features suggestive of legionnaires’ disease and on the exclusion, as far as possible, of other causes of the illness. Plotkin states: "The diagnosis in the second reported patient was based initially on clinical response to erythromycin: such reasoning is untenable." The diagnosis, in fact, rested initially on clinical features suggestive of legionnaires’ disease and particularly on the neurological disturbance which resembled that in a case previously encountered. A case of legionnaires’ disease with dysarthria and ataxia has been reported2 and another case with dysarthria and ataxia persisting long after the acute illness has been seen at Belvidere Hospital, Glasgow (W. C. Love, personal communication). We suggest it would be worthwhile to give erythromycin tc patients with the clinical features we describe pending the results of serological studies and culture of respiratory secretwo cases
tions.
A. W. LEES W. F. TYRRELL
Ruchill Hospital, Glasgow
IgA AND PRIMARY AMŒBIC MENINGOENCEPHALITIS
StR,-Last July a girl of 11 died from primary amoebic meningoencephalitis due to Naegleria fowleri, which developed within 5 days of swimming in a heated indoor pool supplied with water from hot springs. These were later shown to be infected by N. fowleri. Stimulated by the report drom Dr Cursons and colleagues (Jan. 27, p. 233) of low IgA levels in a case of primary amoebic meningoencephalitis similarly related to
bathing, the third
we
have examined serum taken from our patient on of disease and find the immunoglobulins are
day
1 Lees, A W., Tyrrell, W. F. Lancet, 1978, ii, 1336. 2 Gasper, T. M, Farndon, P. A, Davies, R. Br. med. J. 1978, ii, 1611.
within normal limits. The values (normal limits in parentheses) in g/1 were: IgA 1-5(0.9.$), IgG 10 -(8.0-18.0), IgM 1.9 (0.6-2.8). The same serum showed no reaction at a dilution of 1/8 in a fluorescent antibody test against N. fowleri. A full account of this case will be published elsewhere. We thank the department of chemical pathology, University College Hospital, London, for the immunoglobulin estimations.
Royal
United
Hospital,
A. R. R. CAIN
Bath
Public Health Laboratory, Royal United Hospital (North), Bath BA1 3NG
P. G. MANN
Amœbiasis Reference Unit,
Department of Pathology, Hospital for Tropical Diseases,
D. C. WARHURST
London NW1
ABSENCE OF ANTI-ACETYLCHOLINE RECEPTOR ANTIBODIES IN CONGENITAL MYASTHENIA GRAVIS
SIR,-In about 1’c, of patients with myasthenia gravis (M.G.) symptoms and signs are present at birth or are evident shortly after. This congenital form of M.G. differs from "acquired" M.G. of later onset in that males are predominantly affected and the familial incidence is high. Although thymic changes have been reported in the congenital cases, there is no clear evidence that thymectomy or other immunosuppressive treatment is useful. The disease is generally non-progressive. Congenital M.G. needs to be distinguished from familial infantile M.G. in which severe respiratory and feeding difficulties are common, particularly during the neonatal period or during infection. In familial infantile M.G. spontaneous remission can occur.I There is now good evidence that acquired M.G. is an autoimmune disease and that anti-acetylcholine receptor (AChR) antibodies are implicated in causing the disorder of neuromuscular transmission. This antibody is present in over 83% of patients when detected by an immunoprecipitation assay with ’1-bungarotoxin (a-BuTx) labelled extracts of human muscle.2.3 The proportion of patients in whom the antibody is detectable by this assay is smaller in those with pure ocular M.G. (75%) than in those with generalised weakness (>9S%). M.G. sera can also inhibit the binding of x-BuTx to human AChR.3 M.G. immunoglobulin can passively transfer the disease to mice4 and plasma exchange causes a short-lived clinical remission in most patients associated with a temporary reduction in anti-AChR levels.5 In neonatal M.G., a transient illness mothers, occurring in about 12% of babies born to myasthenic maternal anti-AChR antibodies are present.6 We have measured antibodies in six patients with congenital M.G. aged between 6 and 25, all of whom were males. Two of the patients were brothers, and two were the sons of a cousin marriage. Symptoms began at birth or, in the case of one of the brothers, at 18 months. All but one had marked extraocular weakness and all had mild to severe generalised weakness at the time of study. Electromyographic studies in four patients showed evidence of a neuromuscular transmission defect. The response to ’Tensilon’ (edrophonium) was positive, and anticholinesterase treatment was beneficial in all cases. Anti-AChR antibodies, as determined by the immunoprecipitation assay using human AChR, were not detected in any of the six cases. Mean antibody titres were 0-05+0-1nmol/1 (mean + s.D. of three separate determinations on each patient) 1. Fenichel, G. M Archs Neurol 1978, 35, 97. 2. Lindstrom, J. M, Scybold, M E., Lennon, V. A., Whittingham, S., Duane, D. D. Neurology, 1976, 26, 1054 3. Vincent, A., Newsom-Davis, J. in Neurotoxins Tools in neurobiology edited be F. Clementi and F. Ceccarelli) New York in the press. 4. Toyka, E V, Drachman, D B, Griffin, D E, Pestronk, A, Winkelstein, J A., Fischbeck, K H., Kao, I. New Engl J Med, 1977, 296, 125 5. Newsom-Davis, J, Pinching, A. J., Vincent, A, Wilson, S G Neurology, 6.
1978, 28, 266. Keesey, J., Lindstrom, J. M., Cokely,
H New
Engl. J
Med 1977,
296, 55.