1192
Medical
Association, the Heart and Lung Association, the American Cancer Society, and others combined to petition and speak against it at a special
Hearing before a Subcommittee of the House of Representatives." Eventually the product was labelled as a nicotine delivery system and attempts to market it as a tobacco product were abandoned by the company, who meanwhile remain free to promote
conventional cigarettes to the 50 million Americans who still smoke after decades of antismoking policies. There is no cause for complacency in the UK. In 1980, when the Committee on Safety of Medicines licensed the medical use of nicotine chewing gum as an aid to stopping smoking, the decision was based on the usual grounds of safety and efficacy. Not long afterwards the Advisory Committee on Borderline Substances ruled against its use on National Health Service prescriptions, one of the reasons being their doubts about its efficacy, a matter on which they were not competent to judge. The chewing gum (’Nicorette’) was thus the only prescription-only medicine not available on the NHS. From May 1, the 2 mg dose of Nicorette but not the 4 mg dose has been available over the counter. Meanwhile, other less pure and untested nicotine-containing lozenges based on tobacco extracts were allowed to be promoted and sold without medical prescription or evidence of clinical
efficacy Y These examples of regulatory decisions in two countries do not augur well for the initiation of any strategy to replace smoking with a purer source of nicotine. For such a strategy to succeed, it would need to be radical. Suitable nicotine replacement products would have to be made as acceptable and palatable as possible, advertised, actively promoted with health authority endorsement, and given tax advantages over tobacco. Support from the antismoking movement, coupled with progressive restrictions on tobacco might ultimately lead to an effective ban on smoking in public places, which is feasible only if an alternative is available. As tobacco is phased out the emphasis could shift to avoidance of nicotine, if by then it proves to be an unacceptable burden to health. What are the risks of nicotine itself? It has no known role in tobacco-related cancers, neither is it implicated in chronic obstructive lung disease. The possibility of endogenous formation of carcinogenic nitrosamines from nicotine metabolites has been suggested.13 However, this has not been documented and, if it occurs, the amounts would be negligible compared with those present in tobacco and formed when tobacco is burned. While the negligible cardiovascular risks in primary pipe and cigar smokers who have never smoked cigarettes14 may be reassuring as far as slow buccal absorption is concerned, there are various mechanisms through which rapid nicotine absorption from cigarettes might interact with carbon monoxide to exacerbate cardiovascular disease. For example, propranolol largely abolishes the deleterious effects of smoking on mortality following a first heart attack,
indicating that adrenergic mechanisms are involved.15 This observation strongly implicates nicotine, which is the only major smoke component with effects on adrenergic systems. Thus the view of the Chairman and a member of the UK Independent Scientific Committee on Smoking and Health may be oversanguine. They state "That nicotine has a role in the cause of cardiovascular disease has its adherents, but the evidence is not compelling". 16 There is no good reason why a switch from tobacco products to less harmful nicotine delivery systems should not be encouraged. Smoking-related deaths after the year 2000 would fall steadily and substantially if this can be achieved. There is no compelling objection to the recreational and even addictive use of nicotine provided it is not shown to be physically, psychologically, or socially harmful to the user or to
others.
1. Nicotine addiction:
a report of the Surgeon General. Washington, DC: US Department of Health and Human Services, 1988. 2. Abelin T, Buehler A, Muller P, et al. Controlled trial of transdermal nicotine patch in tobacco withdrawal. Lancet 1989; i: 7-10. 3. Feyerabend C, Russell MAH. A rapid gas-liquid chromatographic method for the determination of cotinine and nicotine in biological fluids. J Pharm Pharmacol 1990; 42: 450-52. 4. Russell MAH, Jarvis MJ, Sutherland G, Feyerabend C. Nicotine replacement in smoking cessation: absorption of nicotine vapor from smoke-free cigarettes. JAMA 1987; 257: 3262-65. 5. Office of Population Censuses and Surveys. General Household Survey 1988. London: HM Stationery Office, 1990. 6. Peto R. 7th World Conference on Tobacco and Health, Perth, Western
Australia, 1-5 April, 1990. 7. Fourth Report of the Independent Scientific Committee on Smoking
and
Health. London: HM Stationery Office, 1988. 8. Wald N, Froggatt P, eds. Nicotine, smoking and the low tar programme. Oxford: Oxford University Press, 1989. 9. RJ Reynolds Tobacco Company. Chemical and biological studies on new cigarette prototypes that heat instead of bum tobacco. Winston-Salem, NC: RJ Reynolds Tobacco Co, 1988. 10. DeBethizy JD, Borgerding MF, Doolittle DJ, et al. Chemical and biological studies of a cigarette that heats rather than burns tobacco. J Clin Pharmacol 1990; 30: 755-63. 11. US House of Representatives. Subcommittee on Health and Environment Hearing. Serial no 100-68, July 29, 1988. Washington, DC: US Government Printing Office, 1988. 12. Belcher M, Jarvis MJ, Sutherland G. Nicotine absorption and dependence on an over-the-counter aid to stop smoking. Br Med J
1989; 289: 570. Nicotine, a tobacco-specific precursor for carcinogens. In. Wald N, Froggatt P, eds. Nicotine, smoking and the low tar programme. Oxford: Oxford University Press, 1989: 29-40. 14. Doll R. Prospects for prevention. Br Med J 1983; 286: 445-53. 15. Jafri SM, Tilley BC, Peters R, Schultz LR, Goldstein S. Effects of
13. Hoffman D.
cigarette smoking and propanolol in survivors of acute myocardial infarction. Am J Cardiol 1990; 65: 271-76. 16. Froggatt P, Wald N. The role of nicotine in the tar reduction programme. In: Wald N, Froggatt P, eds. Nicotine, smoking and the low tar programme. Oxford: Oxford University Press, 1989: 229-35.
The autistic dimension A child usually begins to speak at about twelve months. During that first year an internal map of the world is constructed from a mass of incoming sensory data. Once a certain degree of thought, based on this experience, is achieved, the child goes on to acquire a range of communication skills of which language is the most important. Cognitive development therefore depends on the evolution of thought processes that are
1193
themselves dependent on normal brain function. It follows that either damage to the neuronal substrate underlying the evolution of thought or environmental deficiencies that limit sensory experience will lead to cognitive deficits that present clinically as disorders of communication. Such conditions are uncommon and are seen in about 20-40 per 100 000 children. The American
Psychiatric Association, in the revised version of its third Diagnostic and Statistical Manual of Mental Disorders (DSM-IIIR), refers to these conditions as pervasive developmental disorders and identifies autistic disorder as the only recognised subtype to have emerged. Several formes frustes of autism have been described, and some have become established as distinct entities. One such condition is Rett’s syndrome-autistic behaviour, dementia, ataxia, and loss of purposeful hand use in girls under five years of age.1 Some researchers have argued forcefully that a collection of behaviours, first described by Asperger in 19442 a year after Kanner’s original report on autism,3 may also merit a separate diagnostic category.4-6 DSM-IIIR defines autistic disorder as the qualitative impairment of both reciprocal social and non-verbal verbal with a restricted communication, together repertoire of activities and interests, which lead to true intellectual impairment in about three-quarters of those affected; Wing has described these features as a triad of social, language, and behavioural impairment.Asperger’s syndrome has a high degree of behavioural overlap but, in contrast to autistic disorder, has a good social outlook and is not usually characterised by reduced intellect. The World Health Organisation’s tenth International Classification of Diseases (1990) included Asperger’s syndrome as a separate category within pervasive developmental disorders. DSM-IV is now in preparation-should it follow suit? The reasons given for retaining Asperger’s syndrome are both academic and clinical. The preserved intellectual functions of children with this syndrome may allow researchers to study autism without the confounding variable of mental retardation.4 However, the distinction between such normal-intelligence autism and Asperger’s syndrome is, from a pathological viewpoint, falser The clinical reason for maintaining
interaction
and
Asperger’s syndrome give educationalists freedom to identify autistic tendencies in schoolchildren of normal intelligence without the stigma that is attached to a diagnosis of autistic disorder. But the view that autism represents a continuum of behavioural disturbance would encourage a wider discussion of milder forms of autism. Two features of Asperger’s syndrome are said to have defming properties: normal language development6 and motor clumsiness. 10 Cox has maintained that early language acquisition is normal in children with Asperger’s syndrome.6 However, is
to
although acquisition may be relatively unaffected, the process of verbal communication is abnormal—eg, in content with incorrect use of pronouns, stereotyped phrases, and neologisms-and some researchers disagree about the necessity for normal language acquisition as part of the diagnostic check-list for the syndrome.ll Degrees of motor clumsiness may be an unusual feature of some children with autistic features and normal intelligence, but such associated dyspraxia is not sufficient to warrant a separate diagnosis. Is the drive for semantic perfection worth the confusion for parents of children who do not satisfy the predetermined rules by which a diagnosis can be made? The unification of these behaviourally defined states-the autistic dimension-offers an opportunity to draw together conditions that share both neurobiological abnormalities and deficits in communication skills. A broader approach may encourage a more positive attitude towards the outlook of all children with autistic behaviour. L, Gascon GG. Rett syndrome: review and discussion of current diagnostic criteria. J Child Neural 1988; 3: 263-68. 2. Asperger H. Die autistischen Psychopathen im Kindesalter. Archiv Psychiatrie Nerven 1944; 117: 76-136. 3. Kanner L. Autistic disturbances of affective contact. Nerv Child 1943; 2: 1. Bird
217-50. 4. Green J. Is Asperger’s a syndrome? Dev Med Child Neural 1990; 32: 743-47. 5. Wolff S. Asperger’s syndrome. Arch Dis Child 1991; 66: 177-79. 6. Cox AD. Is Asperger’s syndrome a useful diagnosis? Arch Dis Child 1991; 66: 259-62. 7. Wing L. Asperger’s syndrome: a clinical account. Psychol Med 1981; 11: 115-29. 8. Jones PB, Kerwin RW. Left temporal lobe damage in Asperger’s syndrome. Br J Psychiatry 1990; 156: 570-72. 9. Piven J, Berthier ML, Starkstein SE, Nehme E, Pearlson G, Folstein S. Magnetic resonance imaging evidence for a defect of cerebral cortical development in autism. Am J Psychiatry 1990; 147: 734-39. 10. Gillberg C. Asperger syndrome in 23 Swedish children. Dev Med Child Neurol 1989; 31: 520-31. 11. Gillberg C. Gillber IC. Asperger’s syndrome: some epidemiological considerations. J Child Psychol Psychiatry 1989; 30: 631-38.
Antiepileptic drug withdrawal— hawks
or
doves?
Pharmacological control of seizures can be expected to 90% of people with epilepsyl and, in a substantial proportion of these individuals, antiepileptic drug treatment can eventually be in up
withdrawn.2--6 In children remission rates of over 75%
consistently reported in those who have been seizure free for 2 years.6-9 The outcome in adults with epilepsy is harder to detennine,2-3,S partly because of variations in inclusion criteria and in study designs are
several decades in different countries.10 Poor prognostic factors have been identified, especially long duration of epilepsy, neurological abnormalities, complex partial seizures, onset in adulthood, and treatment with more than one antiepileptic agent. The difficulty for doctors arises when they are confronted by a patient who has not had a seizure for a considerable time. The hawks will push ahead with antiepileptic drug withdrawal after 2 years’ freedom over
Medical
Association, the Heart and Lung Association, the American Cancer Society, and others combined to petition and speak against it at a special
Hearing before a Subcommittee of the House of Representatives." Eventually the product was labelled as a nicotine delivery system and attempts to market it as a tobacco product were abandoned by the company, who meanwhile remain free to promote
conventional cigarettes to the 50 million Americans who still smoke after decades of antismoking policies. There is no cause for complacency in the UK. In 1980, when the Committee on Safety of Medicines licensed the medical use of nicotine chewing gum as an aid to stopping smoking, the decision was based on the usual grounds of safety and efficacy. Not long afterwards the Advisory Committee on Borderline Substances ruled against its use on National Health Service prescriptions, one of the reasons being their doubts about its efficacy, a matter on which they were not competent to judge. The chewing gum (’Nicorette’) was thus the only prescription-only medicine not available on the NHS. From May 1, the 2 mg dose of Nicorette but not the 4 mg dose has been available over the counter. Meanwhile, other less pure and untested nicotine-containing lozenges based on tobacco extracts were allowed to be promoted and sold without medical prescription or evidence of clinical
efficacy Y These examples of regulatory decisions in two countries do not augur well for the initiation of any strategy to replace smoking with a purer source of nicotine. For such a strategy to succeed, it would need to be radical. Suitable nicotine replacement products would have to be made as acceptable and palatable as possible, advertised, actively promoted with health authority endorsement, and given tax advantages over tobacco. Support from the antismoking movement, coupled with progressive restrictions on tobacco might ultimately lead to an effective ban on smoking in public places, which is feasible only if an alternative is available. As tobacco is phased out the emphasis could shift to avoidance of nicotine, if by then it proves to be an unacceptable burden to health. What are the risks of nicotine itself? It has no known role in tobacco-related cancers, neither is it implicated in chronic obstructive lung disease. The possibility of endogenous formation of carcinogenic nitrosamines from nicotine metabolites has been suggested.13 However, this has not been documented and, if it occurs, the amounts would be negligible compared with those present in tobacco and formed when tobacco is burned. While the negligible cardiovascular risks in primary pipe and cigar smokers who have never smoked cigarettes14 may be reassuring as far as slow buccal absorption is concerned, there are various mechanisms through which rapid nicotine absorption from cigarettes might interact with carbon monoxide to exacerbate cardiovascular disease. For example, propranolol largely abolishes the deleterious effects of smoking on mortality following a first heart attack,
indicating that adrenergic mechanisms are involved.15 This observation strongly implicates nicotine, which is the only major smoke component with effects on adrenergic systems. Thus the view of the Chairman and a member of the UK Independent Scientific Committee on Smoking and Health may be oversanguine. They state "That nicotine has a role in the cause of cardiovascular disease has its adherents, but the evidence is not compelling". 16 There is no good reason why a switch from tobacco products to less harmful nicotine delivery systems should not be encouraged. Smoking-related deaths after the year 2000 would fall steadily and substantially if this can be achieved. There is no compelling objection to the recreational and even addictive use of nicotine provided it is not shown to be physically, psychologically, or socially harmful to the user or to
others.
1. Nicotine addiction:
a report of the Surgeon General. Washington, DC: US Department of Health and Human Services, 1988. 2. Abelin T, Buehler A, Muller P, et al. Controlled trial of transdermal nicotine patch in tobacco withdrawal. Lancet 1989; i: 7-10. 3. Feyerabend C, Russell MAH. A rapid gas-liquid chromatographic method for the determination of cotinine and nicotine in biological fluids. J Pharm Pharmacol 1990; 42: 450-52. 4. Russell MAH, Jarvis MJ, Sutherland G, Feyerabend C. Nicotine replacement in smoking cessation: absorption of nicotine vapor from smoke-free cigarettes. JAMA 1987; 257: 3262-65. 5. Office of Population Censuses and Surveys. General Household Survey 1988. London: HM Stationery Office, 1990. 6. Peto R. 7th World Conference on Tobacco and Health, Perth, Western
Australia, 1-5 April, 1990. 7. Fourth Report of the Independent Scientific Committee on Smoking
and
Health. London: HM Stationery Office, 1988. 8. Wald N, Froggatt P, eds. Nicotine, smoking and the low tar programme. Oxford: Oxford University Press, 1989. 9. RJ Reynolds Tobacco Company. Chemical and biological studies on new cigarette prototypes that heat instead of bum tobacco. Winston-Salem, NC: RJ Reynolds Tobacco Co, 1988. 10. DeBethizy JD, Borgerding MF, Doolittle DJ, et al. Chemical and biological studies of a cigarette that heats rather than burns tobacco. J Clin Pharmacol 1990; 30: 755-63. 11. US House of Representatives. Subcommittee on Health and Environment Hearing. Serial no 100-68, July 29, 1988. Washington, DC: US Government Printing Office, 1988. 12. Belcher M, Jarvis MJ, Sutherland G. Nicotine absorption and dependence on an over-the-counter aid to stop smoking. Br Med J
1989; 289: 570. Nicotine, a tobacco-specific precursor for carcinogens. In. Wald N, Froggatt P, eds. Nicotine, smoking and the low tar programme. Oxford: Oxford University Press, 1989: 29-40. 14. Doll R. Prospects for prevention. Br Med J 1983; 286: 445-53. 15. Jafri SM, Tilley BC, Peters R, Schultz LR, Goldstein S. Effects of
13. Hoffman D.
cigarette smoking and propanolol in survivors of acute myocardial infarction. Am J Cardiol 1990; 65: 271-76. 16. Froggatt P, Wald N. The role of nicotine in the tar reduction programme. In: Wald N, Froggatt P, eds. Nicotine, smoking and the low tar programme. Oxford: Oxford University Press, 1989: 229-35.
The autistic dimension A child usually begins to speak at about twelve months. During that first year an internal map of the world is constructed from a mass of incoming sensory data. Once a certain degree of thought, based on this experience, is achieved, the child goes on to acquire a range of communication skills of which language is the most important. Cognitive development therefore depends on the evolution of thought processes that are
1193
themselves dependent on normal brain function. It follows that either damage to the neuronal substrate underlying the evolution of thought or environmental deficiencies that limit sensory experience will lead to cognitive deficits that present clinically as disorders of communication. Such conditions are uncommon and are seen in about 20-40 per 100 000 children. The American
Psychiatric Association, in the revised version of its third Diagnostic and Statistical Manual of Mental Disorders (DSM-IIIR), refers to these conditions as pervasive developmental disorders and identifies autistic disorder as the only recognised subtype to have emerged. Several formes frustes of autism have been described, and some have become established as distinct entities. One such condition is Rett’s syndrome-autistic behaviour, dementia, ataxia, and loss of purposeful hand use in girls under five years of age.1 Some researchers have argued forcefully that a collection of behaviours, first described by Asperger in 19442 a year after Kanner’s original report on autism,3 may also merit a separate diagnostic category.4-6 DSM-IIIR defines autistic disorder as the qualitative impairment of both reciprocal social and non-verbal verbal with a restricted communication, together repertoire of activities and interests, which lead to true intellectual impairment in about three-quarters of those affected; Wing has described these features as a triad of social, language, and behavioural impairment.Asperger’s syndrome has a high degree of behavioural overlap but, in contrast to autistic disorder, has a good social outlook and is not usually characterised by reduced intellect. The World Health Organisation’s tenth International Classification of Diseases (1990) included Asperger’s syndrome as a separate category within pervasive developmental disorders. DSM-IV is now in preparation-should it follow suit? The reasons given for retaining Asperger’s syndrome are both academic and clinical. The preserved intellectual functions of children with this syndrome may allow researchers to study autism without the confounding variable of mental retardation.4 However, the distinction between such normal-intelligence autism and Asperger’s syndrome is, from a pathological viewpoint, falser The clinical reason for maintaining
interaction
and
Asperger’s syndrome give educationalists freedom to identify autistic tendencies in schoolchildren of normal intelligence without the stigma that is attached to a diagnosis of autistic disorder. But the view that autism represents a continuum of behavioural disturbance would encourage a wider discussion of milder forms of autism. Two features of Asperger’s syndrome are said to have defming properties: normal language development6 and motor clumsiness. 10 Cox has maintained that early language acquisition is normal in children with Asperger’s syndrome.6 However, is
to
although acquisition may be relatively unaffected, the process of verbal communication is abnormal—eg, in content with incorrect use of pronouns, stereotyped phrases, and neologisms-and some researchers disagree about the necessity for normal language acquisition as part of the diagnostic check-list for the syndrome.ll Degrees of motor clumsiness may be an unusual feature of some children with autistic features and normal intelligence, but such associated dyspraxia is not sufficient to warrant a separate diagnosis. Is the drive for semantic perfection worth the confusion for parents of children who do not satisfy the predetermined rules by which a diagnosis can be made? The unification of these behaviourally defined states-the autistic dimension-offers an opportunity to draw together conditions that share both neurobiological abnormalities and deficits in communication skills. A broader approach may encourage a more positive attitude towards the outlook of all children with autistic behaviour. L, Gascon GG. Rett syndrome: review and discussion of current diagnostic criteria. J Child Neural 1988; 3: 263-68. 2. Asperger H. Die autistischen Psychopathen im Kindesalter. Archiv Psychiatrie Nerven 1944; 117: 76-136. 3. Kanner L. Autistic disturbances of affective contact. Nerv Child 1943; 2: 1. Bird
217-50. 4. Green J. Is Asperger’s a syndrome? Dev Med Child Neural 1990; 32: 743-47. 5. Wolff S. Asperger’s syndrome. Arch Dis Child 1991; 66: 177-79. 6. Cox AD. Is Asperger’s syndrome a useful diagnosis? Arch Dis Child 1991; 66: 259-62. 7. Wing L. Asperger’s syndrome: a clinical account. Psychol Med 1981; 11: 115-29. 8. Jones PB, Kerwin RW. Left temporal lobe damage in Asperger’s syndrome. Br J Psychiatry 1990; 156: 570-72. 9. Piven J, Berthier ML, Starkstein SE, Nehme E, Pearlson G, Folstein S. Magnetic resonance imaging evidence for a defect of cerebral cortical development in autism. Am J Psychiatry 1990; 147: 734-39. 10. Gillberg C. Asperger syndrome in 23 Swedish children. Dev Med Child Neurol 1989; 31: 520-31. 11. Gillberg C. Gillber IC. Asperger’s syndrome: some epidemiological considerations. J Child Psychol Psychiatry 1989; 30: 631-38.
Antiepileptic drug withdrawal— hawks
or
doves?
Pharmacological control of seizures can be expected to 90% of people with epilepsyl and, in a substantial proportion of these individuals, antiepileptic drug treatment can eventually be in up
withdrawn.2--6 In children remission rates of over 75%
consistently reported in those who have been seizure free for 2 years.6-9 The outcome in adults with epilepsy is harder to detennine,2-3,S partly because of variations in inclusion criteria and in study designs are
several decades in different countries.10 Poor prognostic factors have been identified, especially long duration of epilepsy, neurological abnormalities, complex partial seizures, onset in adulthood, and treatment with more than one antiepileptic agent. The difficulty for doctors arises when they are confronted by a patient who has not had a seizure for a considerable time. The hawks will push ahead with antiepileptic drug withdrawal after 2 years’ freedom over
