- Email: [email protected]
EPILEPSY AND INSANITY
756
analysis departs from the data. We feel that we have reached similar conclusions to Williams’ and by using clearer, simpler analysis. A complex interaction is only worth demonstrating if it leads to an illuminating hypothesis or to a specific, additional conclusion. Dr Hehir (July 14, p 104) draws attention to our social classification of women by their husband’s or father’s occupation. There are two problems about adopting a different approach. First, the current classification of occupations developed for men’s jobs does not cover women’s employment very satisfactorily; in particular, it would be difficult to code part-time occupations. Secondly, and more practically, the data set used, which has been in existence since 1965, collects information on whether women have been in paid work in pregnancy, but not on their actual occupation.
J. F. MURPHY of Child Health, Welsh National School of Medicine, Cardiff CF4 4XN
Department
R. NEWCOMBE M. DAUNCEY J. GORCIA
D. ELBOURNE
EPILEPSY AND INSANITY
SIR,-I read with interest the letter by Dr Fenwick and his twenty co-signatories (Sept 1, p 528). The Sullivan case does indeed raise issues of concern to all doctors engaged in medicolegal work. The issues are various and difficult but the complexities are legal rather than medical. On the question of automatism the Law has now manoeuvred itself into an untenable position. Mr Sullivan was able, by pleading "guilty", to receive a more lenient disposal than if he had pleaded "not guilty by reason of insanity". Furthermore, he was allowed to plead guilty even when considerable evidence was available to demonstrate that he did not have the necessary mens rea in relation to the assault, because he was in an automatic state. The definition of insanity is again legal rather than medical-as is that-of the other relevant concept, abnormality of mind. Doctors become involved in such cases to assist the law with the dilemma it has created for itself. The Butler recommendations of 1975 should be urgently implemented, and judges should be given discretionary sentencing powers in cases which now must be dealt with by a mandatory hospital disposal-the so-called "special verdict". Doctors would then be able, in such cases, to add observations as to the need for medical treatment on a voluntary or formal basis. They would thus be able to make helpful recommendations to the court about disposal rather than be forced into abstract discussions about the meaning of insanity and other such legal concepts. If the law needs revision suitable legislation will no doubt follow but a simple manoeuvre in relation to mandatory hospital sentences could clarify the medical and legal issues as separate entities. This would provide an interim workable solution while the legislators give serious consideration to the revision of the law on automatism, insanity, and special verdicts, which seems to have become essential. David Westbury Centre, Winterton Hospital, Sedgefield, Durham
MARION SWAN
NEUTROPHIL ACTIVATION AFTER MYOCARDIAL
INFARCTION
SIR,-Much attention has been given to the possible pathogenic role of reactive oxygen metabolites in heart disease. 1,2 These metabolites include 02 , OH., OC1-, and 102. Neutrophils, cells that can produce these metabolites, rapidly infiltrate the myocardium in large numbers after infarction, but there is no evidence in man that they are detrimental to the myocardium. However, Romson et al have reported that reduction of cellular infiltration after myocardial infarction in laboratory animals greatly reduces infarct size.3 During a study of the oxidation of adrenaline through the adrenochrome pathway by neutrophils,4aprocess which involves reactive oxygen metabolites, we discovered a catalytic "oxidase" in the serum of patients after myocardial infarction. Certain stimuli-eg, a chemotactic peptide acting through a rise in
Relation between oxidase activity in infarction.
serum
and
myocardial
Serum and distilled water (1: ) were incubated at 37°C for 2 h in the presence and absence of adrenaline (1 mmol) in 1ml. The samples were centrifuged at 12 000 rpm for 2 min and A480 measured to assess adrenochrome formation. (e 480 = 4020 mol+ cm). Oxidase activity was expressed in units/1 where 1 unit umol of adrenaline converted to adrenochrome during incubation (2 h).
intracellular
free
calcium, 5,6
stimulate
the
release
of
myeloperoxidase from neutrophils, and this enzyme has properties similar to the "adrenaline oxidase" found in patients’ serum. We have investigated the possibility that this oxidase might be a useful indicator of neutrophil activation within the myocardium, thereby providing a method of assessing reactive-oxygen-metabolite production in myocardial infarction. The oxidase in serum was assayed by measuring the conversion of adrenaline formation was detected adrenochrome. Adrenochrome spectrophotometrically at 480 nm (480=4020 mol-’ cm-’). The results (see figure) were expressed in units/I. The control subjects were healthy laboratory workers (n= 13; age range 21-45 years). The patients studied were those admitted to the coronary-care unit or an acute medical ward with chest pain, and who had myocardial infarction included in the differential diagnosis (n = 6.1; age range 41-85 years). All the patients had serial electrocardiograms (ECGs) and creatine kinase (CK) was measured over a minimum of 3 days. The diagnosis of myocardial infarction was made on the basis of ST-segment elevation, T-wave inversion, Q-wave formation, and an increase in serum CK of over 200 IU/1 within 48 h of admission. On the basis of these criteria the patients with chest pain were separated into 2 groups. Patients in the first group showed evidence of myocardial infarction from both ECG recordings and CK measurements (n=31; mean CK 592 IU/1). These patients had a mean serum-oxidase activity of 170 units/I; 4 patients (open circles in figure) had high serum-oxidase activity on admission, yet an elevated CK was not detected until the day after admission. Patients in the second group showed no evidence of myocardial infarction and were diagnosed as having angina or chest pain of unknown cause (n = 28; mean CK 72 IU/1). These patients had a mean oxidase activity of 100 units/I. 3 patients had ECG evidence of acute myocardial infarction, but the CK remained normal. They had high oxidase activities of 140, 160, and 175 U/l, and severe arrhythmias developed in all 3 within 24 h of admission to hospital. Serum oxidase activity was higher in group 1 (myocardial infarction) than in the control group (p<0- 001) or group 2 (angina and undiagnosed chest pain) (p<0 001), and was higher in group 2 than the control group (p<0001). to
The nature of the oxidase is unknown. It may be myeloperoxidase secreted from neutrophil granules, but a stable oxidant such as OC1" or H2 O2 or a product of these reactive oxygen metabolites cannot be ruled out. Our results provide the basis for an early, rapid, and non-invasive assessment of neutrophil activation after
analysis departs from the data. We feel that we have reached similar conclusions to Williams’ and by using clearer, simpler analysis. A complex interaction is only worth demonstrating if it leads to an illuminating hypothesis or to a specific, additional conclusion. Dr Hehir (July 14, p 104) draws attention to our social classification of women by their husband’s or father’s occupation. There are two problems about adopting a different approach. First, the current classification of occupations developed for men’s jobs does not cover women’s employment very satisfactorily; in particular, it would be difficult to code part-time occupations. Secondly, and more practically, the data set used, which has been in existence since 1965, collects information on whether women have been in paid work in pregnancy, but not on their actual occupation.
J. F. MURPHY of Child Health, Welsh National School of Medicine, Cardiff CF4 4XN
Department
R. NEWCOMBE M. DAUNCEY J. GORCIA
D. ELBOURNE
EPILEPSY AND INSANITY
SIR,-I read with interest the letter by Dr Fenwick and his twenty co-signatories (Sept 1, p 528). The Sullivan case does indeed raise issues of concern to all doctors engaged in medicolegal work. The issues are various and difficult but the complexities are legal rather than medical. On the question of automatism the Law has now manoeuvred itself into an untenable position. Mr Sullivan was able, by pleading "guilty", to receive a more lenient disposal than if he had pleaded "not guilty by reason of insanity". Furthermore, he was allowed to plead guilty even when considerable evidence was available to demonstrate that he did not have the necessary mens rea in relation to the assault, because he was in an automatic state. The definition of insanity is again legal rather than medical-as is that-of the other relevant concept, abnormality of mind. Doctors become involved in such cases to assist the law with the dilemma it has created for itself. The Butler recommendations of 1975 should be urgently implemented, and judges should be given discretionary sentencing powers in cases which now must be dealt with by a mandatory hospital disposal-the so-called "special verdict". Doctors would then be able, in such cases, to add observations as to the need for medical treatment on a voluntary or formal basis. They would thus be able to make helpful recommendations to the court about disposal rather than be forced into abstract discussions about the meaning of insanity and other such legal concepts. If the law needs revision suitable legislation will no doubt follow but a simple manoeuvre in relation to mandatory hospital sentences could clarify the medical and legal issues as separate entities. This would provide an interim workable solution while the legislators give serious consideration to the revision of the law on automatism, insanity, and special verdicts, which seems to have become essential. David Westbury Centre, Winterton Hospital, Sedgefield, Durham
MARION SWAN
NEUTROPHIL ACTIVATION AFTER MYOCARDIAL
INFARCTION
SIR,-Much attention has been given to the possible pathogenic role of reactive oxygen metabolites in heart disease. 1,2 These metabolites include 02 , OH., OC1-, and 102. Neutrophils, cells that can produce these metabolites, rapidly infiltrate the myocardium in large numbers after infarction, but there is no evidence in man that they are detrimental to the myocardium. However, Romson et al have reported that reduction of cellular infiltration after myocardial infarction in laboratory animals greatly reduces infarct size.3 During a study of the oxidation of adrenaline through the adrenochrome pathway by neutrophils,4aprocess which involves reactive oxygen metabolites, we discovered a catalytic "oxidase" in the serum of patients after myocardial infarction. Certain stimuli-eg, a chemotactic peptide acting through a rise in
Relation between oxidase activity in infarction.
serum
and
myocardial
Serum and distilled water (1: ) were incubated at 37°C for 2 h in the presence and absence of adrenaline (1 mmol) in 1ml. The samples were centrifuged at 12 000 rpm for 2 min and A480 measured to assess adrenochrome formation. (e 480 = 4020 mol+ cm). Oxidase activity was expressed in units/1 where 1 unit umol of adrenaline converted to adrenochrome during incubation (2 h).
intracellular
free
calcium, 5,6
stimulate
the
release
of
myeloperoxidase from neutrophils, and this enzyme has properties similar to the "adrenaline oxidase" found in patients’ serum. We have investigated the possibility that this oxidase might be a useful indicator of neutrophil activation within the myocardium, thereby providing a method of assessing reactive-oxygen-metabolite production in myocardial infarction. The oxidase in serum was assayed by measuring the conversion of adrenaline formation was detected adrenochrome. Adrenochrome spectrophotometrically at 480 nm (480=4020 mol-’ cm-’). The results (see figure) were expressed in units/I. The control subjects were healthy laboratory workers (n= 13; age range 21-45 years). The patients studied were those admitted to the coronary-care unit or an acute medical ward with chest pain, and who had myocardial infarction included in the differential diagnosis (n = 6.1; age range 41-85 years). All the patients had serial electrocardiograms (ECGs) and creatine kinase (CK) was measured over a minimum of 3 days. The diagnosis of myocardial infarction was made on the basis of ST-segment elevation, T-wave inversion, Q-wave formation, and an increase in serum CK of over 200 IU/1 within 48 h of admission. On the basis of these criteria the patients with chest pain were separated into 2 groups. Patients in the first group showed evidence of myocardial infarction from both ECG recordings and CK measurements (n=31; mean CK 592 IU/1). These patients had a mean serum-oxidase activity of 170 units/I; 4 patients (open circles in figure) had high serum-oxidase activity on admission, yet an elevated CK was not detected until the day after admission. Patients in the second group showed no evidence of myocardial infarction and were diagnosed as having angina or chest pain of unknown cause (n = 28; mean CK 72 IU/1). These patients had a mean oxidase activity of 100 units/I. 3 patients had ECG evidence of acute myocardial infarction, but the CK remained normal. They had high oxidase activities of 140, 160, and 175 U/l, and severe arrhythmias developed in all 3 within 24 h of admission to hospital. Serum oxidase activity was higher in group 1 (myocardial infarction) than in the control group (p<0- 001) or group 2 (angina and undiagnosed chest pain) (p<0 001), and was higher in group 2 than the control group (p<0001). to
The nature of the oxidase is unknown. It may be myeloperoxidase secreted from neutrophil granules, but a stable oxidant such as OC1" or H2 O2 or a product of these reactive oxygen metabolites cannot be ruled out. Our results provide the basis for an early, rapid, and non-invasive assessment of neutrophil activation after