- Email: [email protected]
THE FUNCTION OF ADRENALINE
561
antigens (complement-dependent cytotoxicity, immunofluorescence, or enzyme-linked immunoassays) are highly sensitive but, for the most part, they are not quantitatively of immunohistochemical fixed tissue sections. They techniques applied of the involve building up multilayered antibody usually "sandwiches" with amplification steps incorporated into one or more of the layers. The quantity of final reaction product visible on the slide then depends as much on the effectiveness of amplification as on the amount of original antigen present. In these circumstances, scrupulous attention to methodological controls is essential. Any series of sections should include at least one that has been through the complete sequence of processing steps, differing from the experimental set only by the substitution of an irrelevant accurate.
This is
even more true
to
frozen
or
antibody (monoclonal or conventional, as appropriate) matching the test reagent for species of origin, as the first layer of the sandwich. Without such obsessional attention to detail, investigators may be misled by the very power of the techniques now available to them.
THE FUNCTION OF ADRENALINE A PAPER by Wortsman and colleaguesl raises again the enigma of adrenaline (epinephrine). Extraordinarily high plasma adrenaline concentrations were recorded in patients resuscitated from cardiac arrest: they rose to 300 times normal, whereas plasma noradrenaline rose only 10-fold. So cardiac arrest, like hypoglycaemia2,3 and haemorrhagic
shock,4
seems to stimulate near-maximum secretion of adrenaline. What function can this serve? Unlike the release of noradrenaline from sympathetic nerves and of most other hormones, the release of adrenaline from the adrenal medulla is not subject to any negative feedback mechanisms. Furthermore, the potential for an explosive increase in release is enhanced by at least two positive feedback circuits. Adrenaline stimulates the renin angiotensin system (a &bgr;-receptor-mediated effect), and angiotensin II facilitates release of catecholamines from both adrenal medulla and sympathetic nerves.5,6 Adrenaline also stimulates &bgr;2 receptors on the pituitary gland, causing corticotropin release,’ and corticotropin can stimulate the adrenal medulla (as well as cortex).8,9 That these amplification loops play a role in vivo is indirectly suggested by the magnitude of adrenaline release after cardiac arrest (up to 36 ng/ml);’ concentrations of this order are not often found even in patients with large catecholamine secreting
1 Wortsman J, Frank S,
Cryer PE. Adrenomedullary response to maximal stress in humans. Am J Med 1984; 77: 779-84. 2 Garber AJ, Cryer PE, Santiago JV, Haymond MW, Pagliara AS, Kipnis DM. The role of adrenergic mechanisms in the substrate and hormonal response to insulininduced hypoglycaemia in man.J Clin Invest 1976, 58: 7-15. 3 Cryer PE Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system
4 Benedict
DG.
Plasma
and
adrenaline
dopamine-&bgr;-hydroxylase activity in patients with shock due to septicaemia, trauma and hemorrhage, Quart J Med 1978, 48: 1-20. 5 Hughes J, Roth RH. Evidence that angiotensin enhances transmitter release during synpathetic nerve stimulation. Br J Pharmacol 1971; 41: 239-55. 6 Peach MJ, Cline WH, Watts DT. Release of adrenal catecholamines by angiotensin II. concentrations
and
Circ Res 1966, 19: 571-78. Reisine TD, Heisler S, Hook VYH, Axelrod J. Activation of &bgr;2 adrenergic receptors on mouse anterior pituitary tumour cells increases cyclic AMP synthesis and adrenocorticotropin release J Neurosci 1983, 3: 725-32. 8 Catchley JAJH, Ellis P, Henderson CG, Ungar A. The role of the pituitary adrenocorticol axis in reflex responses of the adrenal medulla of the dog. J Physiol
11
12.
13.
14. 15.
1982, 323: 533-41.
9 Ungar A, Phillips JH Regulation of 787-843.
the adrenal medulla
Physiol
Rev
1983; 63:
EL, Tarazi RC, Clifford RW, Stewart BH. Circulating and urinary catecholamines in phaeochromocytoma: diagnostic and pathophysiologic implications. N Engl J Med 1979; 301: 682-86. Brown MJ, Allison DJ, Jenner DA, Lewis PJ, Dollery CT Increased sensitivity and accuracy of phaeochromocytoma diagnosis achieved by use of plasma adrenaline estimations and a pentolinium suppression test. Lancet 1981: i: 174-77. Robertson D, Johnson GA, Robertson RM, et al. Comparative assessment of stimuli that release neuronal and adrenomedullary catecholamines in man Circulation 1979, 59: 637-43 Dimsdale JE, Moss J. Short term catecholamine response to psychological stress. Psychosomatic Med 1980; 42: 493-97. Pearson JW, Redding JS. Epinephrine in cardiac resuscitation. A Heart J 1963; 66: 210-14 Redding JS, Pearson JW. Resuscitation from ventricular fibrillation-drug therapy. JAMA 1968, 203: 93-98 Iseri LT, Humphrey SB, Siver EJ. Prehospital brady-assytolic cardiac arrest. Ann Intern Med 1978; 88: 741-45.
10 Bravo
N Engl J Med 1980; 303:
CR, Grahame-Smith
436-44. noradrenaline
tumours, 10, I so maximum release of the glands’ stores of catecholamines does seem to require intact release mechanisms. In the response to more mundane stresses the sympathetic nervous system is more important than the adrenal medulla, because of the much higher (and more rapidly achieved) concentration of noradrenaline in the synaptic cleft. This can easily be confirmed by comparison of the relative increases of plasma noradrenaline and adrenaline concentrations during standardised stress tests such as mental arithmetic and the cold pressor test.12 In everyday stresses, however, it is probably the element of fright or apprehension that is required to stimulate adrenaline release, and this (almost by definition) is hard to reproduce in standardised laboratory tests; high concentrations of adrenaline have been detected in some patients undergoing invasive investigations and in medical interns giving their first public case presentations. 11,13 Yet, even if a sudden fright does cause a transient increase in plasma adrenaline concentration, the experience ofa "missed heart beat" teaches us that it must be the cardiac nerves and not adrenaline that is reponsible, since there is a delay of almost one minute between adrenaline release (or injection) and its arrival in cardiac synaptic clefts. Such observations leave adrenaline with an uncertain role in man. Most endocrine systems are vivid support for Aristotle’s concept of the-golden mean, in that diseases are associated with states of both hormone insufficiency and excess. Adrenaline replacement therapy, by contrast, finds no place in a handbook of therapeutics. Is it then purely vestigial, or is it the Sydney Carton of hormones-a bystander except at moments of catastrophe? It is hard to be certain whether such occasional massive release of adrenaline is beneficial. The concentrations of plasma adrenaline measured immediately after cardiac arrest were about 7-fold lower than the subsequent concentrations recorded after some patients had received adrenaline injections.1 There was, however, considerable overlap between the two sets of measurements. Prospective clinical trials of emergency drug therapy are notoriously difficult and scarce, and there is little firm evidence that adrenaline helps survival from cardiac arrest. Large doses of adrenaline increase survival from ventricular fibrillation in dogs14 and there is anecdotal evidence ofa beneficial effect in man.15,16 But high concentrations of adrenaline, usually of iatrogenic origin, have as many risks as benefits, cardiac arrhythmias and renal failure being the best known. For this reason the therapeutic applications of adrenaline have become much fewer since a-receptor agonists became unfashionable for circulatory shock, and its &bgr;-agonist properties were subsumed by the supposedly safer partial &bgr;2-agonists such as salbutamol. Cardiac arrest and anaphylaxis are among the dwindling indications before adrenaline. While this trend is
16
562 there are few formal comparisons of adrenaline and newer drugs in either circulatory failure or asthma; indeed, the continued use of adrenaline in extremiis a recognition of its potential superiority as a full agonist acting at all populations of adrenoreceptors. The mention of asthma and adrenaline raises the most curious paradox of all concerning the physiological role of adrenaline. For the dyspnoea of acute asthma seems not to be recognised by the adrenal medulla as a stress: no rise in plasma adrenaline is detectable either in status asthmaticus or in exercise-induced bronchospasm-although noradrenaline release is stimulated several-fold. 17,18 Yet the bronchioles are the tissue with the greatest density of adrenaline’s "natural receptors"-(2 receptors. This paradox remains to be resolved along with the related question of why &bgr;2 blockers provoke bronchospasm if there is (apparently) insufficient adrenaline to cause tonic stimulation of bronchial &bgr; receptors. These receptors are not innervated (and therefore not exposed to very high noradrenaline concentrations) and have a several-hundred-fold greater affinity for adrenaline than for noradrenaline. Perhaps even if the bronchi themselves are not innervated, the spillover of noradrenaline from vascular nerve endings creates a sufficient perisynaptic noradrenaline concentration for stimulation of nearby bronchial &bgr; receptors. It is now apparent that spillover of noradrenaline from a tissue is poorly correlated with the richness of sympathetic innervation, 19,20 and the lung indeed contributes more than any other organ to circulating noradrenaline. 19 So, in their desertion of adrenaline, doctors could claim to be following evolutionary advice to keep one of their most powerful drugs in reserve for the direst emergencies.
probably to be welcomed,
POST-TRAUMATIC STRESS DISORDER ONE of the most interesting new classifications in the American Psychiatric Association’s latest Diagnostic and Statistical Manual (DSM III) is "post-traumatic stress disorder". Officially the designation 309-81 refers to "The development of characteristic symptoms following a psychologically traumatic event that is generally outside the range of human experience".’ The main symptoms are a reexperiencing of the traumatic event itself, often with intrusive daytime recollection or with dreams and nightmares, reduced involvement with the outside world, with feelings of detachment and loss of interest, and the presentation of various autonomic, cognitive, and dysphoric
symptoms.
diagnosis, appearing in the DSM III almost as if it new discovery, has come to the attention of psychiatrists in Americal partly through the growing catalogue of psychopathological disorders recorded subsequent to the Korean and Vietnam wars. In Britain psychiatrists will recognise this as a disorder with a very long and chequered history,2commonly referred to as postThis
were
a
17. Ind PW, Causon RC, Brown MJ, Barnes PJ Circulating catecholamines in acute asthma. Br Med J 1985; 290: 267-69 18 Barnes PJ, Brown MJ, Silverman M, Dollery CT. Circulating catecholamines in exercise and hyperventilation induced asthma Thorax 1981; 36: 435-40. 19 Esler M, Jennings G, Korner P, et al Total and organ specific noradrenaline plasma kinetics in essential hypertension. Clin Exp Hyper 1984; 86: 507-22. 20 Brown MJ, Jenner DA, Allison DJ, Dollery CT. Variations in individual organ release of noradrenaline measured by an improved radioenzymatic technique Clin Sci 1981, 61: 585-90. 1 American Psychiatric Association. DSM III Washington, DC: APA, 1980. 2. Trimble MR. Post-traumatic neurosis. Chichester: John Wiley, 1981
traumatic neurosis or accident neurosis. This condition, which costs individuals, governments, communities, and insurance companies vast sums in lost earnings or compensation payments, has curiously been the subject of very little research, although most physicians must have encountered patients in whom such symptoms have developed after accidents, often of a minor nature. The main arena where the condition is discussed is the medicolegal circus, in which it is customary to find two eminent physicians-one appearing for the plaintiff, the other for the defence-giving contradictory views not only about the status of the patient’s symptoms but also about their aetiology and pathogenesis. Many of the arguments relate to the question of malingering, and whether the patient is producing symptoms for personal financial gain. The author most often cited by those springing to the defence of insurance companies is the late Henry Miller, who was led to the conclusion that accident neurosis (the term he preferred) was "not the result of the accident but a concomitant of the compensation and the manifestation of the hope of financial gain".3 Thus it is confidently asserted that, once there has been a financial settlement, the patient will immediately return to work. Tarsh and Royston have now examined this question, after financial settlement, in 35 litigants, all of whom had severe somatic symptoms in the absence of clearly defined physical ills. In contrast to Miller’s cases, these
patients were referred by the plaintiffs’ solicitors. They were traced after a substantial amount of detective work and interviewed regarding their settlement and outcome. Amongst the conclusions of Tarsh and Royston, three are of special note. First, "return to work was the exception rather than the rule, and did not occur in two-thirds of those involved". This very clear finding substantiates the results of several other workers including Kellywho, as a conclusion to his own follow-up study, noted "it is not longer justifiable for a neurologist or lawyer to stand up in court and affirm that it is well known that patients with such symptoms immediately return to work after their claim has been settled". Mendelson,6 reviewing the published work in 1982, emphasised several other studies that substantiate this view, in contrast to the assertions of Miller. Secondly, working on a suggestion of Kelly5 that resentment was a common obstacle in such cases, they noted that claimants reserved most of their wrath for the medicolegal merry-go-round. In particular, patients were distressed by the number of different medical examinations that they had to attend, and the lack of any attempt at treatment. Thirdly, the development of behaviour patterns within the family after the accident seemed more important than any pre-existing personality disorder in contributing to the prolongation of symptoms. This matter, rarely discussed and never examined systematically, is clearly open for future research. In view of the increasing number of studies that emphasise the continuation of post-traumatic neurosis after settlement, it is a wonder that the alternative view, that they will soon recover, continues to be expressed. The designation of "posttraumatic stress disorder" by the American Psychiatric Association, and the growing body of published work, should stimulate clinicians to heed this syndrome so frequently neglected outside the high courts. 3 Miller H Accident 4 Tarsh
neurosis. Br Med J 1961, i: 919-25, 992-98. MJ, Royston C A follow-up study of accident neurosis. Br J Psychiatry 1985
146: 18-25 5. Kelly R The post-traumatic syndrome. Roy Soc Med 1981, 24: 242-44. 6. Mendelson G Not "cured by a verdict"—effect of legal settlement on compensation claimants Med J Aust 1982; ii: 132-34.
antigens (complement-dependent cytotoxicity, immunofluorescence, or enzyme-linked immunoassays) are highly sensitive but, for the most part, they are not quantitatively of immunohistochemical fixed tissue sections. They techniques applied of the involve building up multilayered antibody usually "sandwiches" with amplification steps incorporated into one or more of the layers. The quantity of final reaction product visible on the slide then depends as much on the effectiveness of amplification as on the amount of original antigen present. In these circumstances, scrupulous attention to methodological controls is essential. Any series of sections should include at least one that has been through the complete sequence of processing steps, differing from the experimental set only by the substitution of an irrelevant accurate.
This is
even more true
to
frozen
or
antibody (monoclonal or conventional, as appropriate) matching the test reagent for species of origin, as the first layer of the sandwich. Without such obsessional attention to detail, investigators may be misled by the very power of the techniques now available to them.
THE FUNCTION OF ADRENALINE A PAPER by Wortsman and colleaguesl raises again the enigma of adrenaline (epinephrine). Extraordinarily high plasma adrenaline concentrations were recorded in patients resuscitated from cardiac arrest: they rose to 300 times normal, whereas plasma noradrenaline rose only 10-fold. So cardiac arrest, like hypoglycaemia2,3 and haemorrhagic
shock,4
seems to stimulate near-maximum secretion of adrenaline. What function can this serve? Unlike the release of noradrenaline from sympathetic nerves and of most other hormones, the release of adrenaline from the adrenal medulla is not subject to any negative feedback mechanisms. Furthermore, the potential for an explosive increase in release is enhanced by at least two positive feedback circuits. Adrenaline stimulates the renin angiotensin system (a &bgr;-receptor-mediated effect), and angiotensin II facilitates release of catecholamines from both adrenal medulla and sympathetic nerves.5,6 Adrenaline also stimulates &bgr;2 receptors on the pituitary gland, causing corticotropin release,’ and corticotropin can stimulate the adrenal medulla (as well as cortex).8,9 That these amplification loops play a role in vivo is indirectly suggested by the magnitude of adrenaline release after cardiac arrest (up to 36 ng/ml);’ concentrations of this order are not often found even in patients with large catecholamine secreting
1 Wortsman J, Frank S,
Cryer PE. Adrenomedullary response to maximal stress in humans. Am J Med 1984; 77: 779-84. 2 Garber AJ, Cryer PE, Santiago JV, Haymond MW, Pagliara AS, Kipnis DM. The role of adrenergic mechanisms in the substrate and hormonal response to insulininduced hypoglycaemia in man.J Clin Invest 1976, 58: 7-15. 3 Cryer PE Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system
4 Benedict
DG.
Plasma
and
adrenaline
dopamine-&bgr;-hydroxylase activity in patients with shock due to septicaemia, trauma and hemorrhage, Quart J Med 1978, 48: 1-20. 5 Hughes J, Roth RH. Evidence that angiotensin enhances transmitter release during synpathetic nerve stimulation. Br J Pharmacol 1971; 41: 239-55. 6 Peach MJ, Cline WH, Watts DT. Release of adrenal catecholamines by angiotensin II. concentrations
and
Circ Res 1966, 19: 571-78. Reisine TD, Heisler S, Hook VYH, Axelrod J. Activation of &bgr;2 adrenergic receptors on mouse anterior pituitary tumour cells increases cyclic AMP synthesis and adrenocorticotropin release J Neurosci 1983, 3: 725-32. 8 Catchley JAJH, Ellis P, Henderson CG, Ungar A. The role of the pituitary adrenocorticol axis in reflex responses of the adrenal medulla of the dog. J Physiol
11
12.
13.
14. 15.
1982, 323: 533-41.
9 Ungar A, Phillips JH Regulation of 787-843.
the adrenal medulla
Physiol
Rev
1983; 63:
EL, Tarazi RC, Clifford RW, Stewart BH. Circulating and urinary catecholamines in phaeochromocytoma: diagnostic and pathophysiologic implications. N Engl J Med 1979; 301: 682-86. Brown MJ, Allison DJ, Jenner DA, Lewis PJ, Dollery CT Increased sensitivity and accuracy of phaeochromocytoma diagnosis achieved by use of plasma adrenaline estimations and a pentolinium suppression test. Lancet 1981: i: 174-77. Robertson D, Johnson GA, Robertson RM, et al. Comparative assessment of stimuli that release neuronal and adrenomedullary catecholamines in man Circulation 1979, 59: 637-43 Dimsdale JE, Moss J. Short term catecholamine response to psychological stress. Psychosomatic Med 1980; 42: 493-97. Pearson JW, Redding JS. Epinephrine in cardiac resuscitation. A Heart J 1963; 66: 210-14 Redding JS, Pearson JW. Resuscitation from ventricular fibrillation-drug therapy. JAMA 1968, 203: 93-98 Iseri LT, Humphrey SB, Siver EJ. Prehospital brady-assytolic cardiac arrest. Ann Intern Med 1978; 88: 741-45.
10 Bravo
N Engl J Med 1980; 303:
CR, Grahame-Smith
436-44. noradrenaline
tumours, 10, I so maximum release of the glands’ stores of catecholamines does seem to require intact release mechanisms. In the response to more mundane stresses the sympathetic nervous system is more important than the adrenal medulla, because of the much higher (and more rapidly achieved) concentration of noradrenaline in the synaptic cleft. This can easily be confirmed by comparison of the relative increases of plasma noradrenaline and adrenaline concentrations during standardised stress tests such as mental arithmetic and the cold pressor test.12 In everyday stresses, however, it is probably the element of fright or apprehension that is required to stimulate adrenaline release, and this (almost by definition) is hard to reproduce in standardised laboratory tests; high concentrations of adrenaline have been detected in some patients undergoing invasive investigations and in medical interns giving their first public case presentations. 11,13 Yet, even if a sudden fright does cause a transient increase in plasma adrenaline concentration, the experience ofa "missed heart beat" teaches us that it must be the cardiac nerves and not adrenaline that is reponsible, since there is a delay of almost one minute between adrenaline release (or injection) and its arrival in cardiac synaptic clefts. Such observations leave adrenaline with an uncertain role in man. Most endocrine systems are vivid support for Aristotle’s concept of the-golden mean, in that diseases are associated with states of both hormone insufficiency and excess. Adrenaline replacement therapy, by contrast, finds no place in a handbook of therapeutics. Is it then purely vestigial, or is it the Sydney Carton of hormones-a bystander except at moments of catastrophe? It is hard to be certain whether such occasional massive release of adrenaline is beneficial. The concentrations of plasma adrenaline measured immediately after cardiac arrest were about 7-fold lower than the subsequent concentrations recorded after some patients had received adrenaline injections.1 There was, however, considerable overlap between the two sets of measurements. Prospective clinical trials of emergency drug therapy are notoriously difficult and scarce, and there is little firm evidence that adrenaline helps survival from cardiac arrest. Large doses of adrenaline increase survival from ventricular fibrillation in dogs14 and there is anecdotal evidence ofa beneficial effect in man.15,16 But high concentrations of adrenaline, usually of iatrogenic origin, have as many risks as benefits, cardiac arrhythmias and renal failure being the best known. For this reason the therapeutic applications of adrenaline have become much fewer since a-receptor agonists became unfashionable for circulatory shock, and its &bgr;-agonist properties were subsumed by the supposedly safer partial &bgr;2-agonists such as salbutamol. Cardiac arrest and anaphylaxis are among the dwindling indications before adrenaline. While this trend is
16
562 there are few formal comparisons of adrenaline and newer drugs in either circulatory failure or asthma; indeed, the continued use of adrenaline in extremiis a recognition of its potential superiority as a full agonist acting at all populations of adrenoreceptors. The mention of asthma and adrenaline raises the most curious paradox of all concerning the physiological role of adrenaline. For the dyspnoea of acute asthma seems not to be recognised by the adrenal medulla as a stress: no rise in plasma adrenaline is detectable either in status asthmaticus or in exercise-induced bronchospasm-although noradrenaline release is stimulated several-fold. 17,18 Yet the bronchioles are the tissue with the greatest density of adrenaline’s "natural receptors"-(2 receptors. This paradox remains to be resolved along with the related question of why &bgr;2 blockers provoke bronchospasm if there is (apparently) insufficient adrenaline to cause tonic stimulation of bronchial &bgr; receptors. These receptors are not innervated (and therefore not exposed to very high noradrenaline concentrations) and have a several-hundred-fold greater affinity for adrenaline than for noradrenaline. Perhaps even if the bronchi themselves are not innervated, the spillover of noradrenaline from vascular nerve endings creates a sufficient perisynaptic noradrenaline concentration for stimulation of nearby bronchial &bgr; receptors. It is now apparent that spillover of noradrenaline from a tissue is poorly correlated with the richness of sympathetic innervation, 19,20 and the lung indeed contributes more than any other organ to circulating noradrenaline. 19 So, in their desertion of adrenaline, doctors could claim to be following evolutionary advice to keep one of their most powerful drugs in reserve for the direst emergencies.
probably to be welcomed,
POST-TRAUMATIC STRESS DISORDER ONE of the most interesting new classifications in the American Psychiatric Association’s latest Diagnostic and Statistical Manual (DSM III) is "post-traumatic stress disorder". Officially the designation 309-81 refers to "The development of characteristic symptoms following a psychologically traumatic event that is generally outside the range of human experience".’ The main symptoms are a reexperiencing of the traumatic event itself, often with intrusive daytime recollection or with dreams and nightmares, reduced involvement with the outside world, with feelings of detachment and loss of interest, and the presentation of various autonomic, cognitive, and dysphoric
symptoms.
diagnosis, appearing in the DSM III almost as if it new discovery, has come to the attention of psychiatrists in Americal partly through the growing catalogue of psychopathological disorders recorded subsequent to the Korean and Vietnam wars. In Britain psychiatrists will recognise this as a disorder with a very long and chequered history,2commonly referred to as postThis
were
a
17. Ind PW, Causon RC, Brown MJ, Barnes PJ Circulating catecholamines in acute asthma. Br Med J 1985; 290: 267-69 18 Barnes PJ, Brown MJ, Silverman M, Dollery CT. Circulating catecholamines in exercise and hyperventilation induced asthma Thorax 1981; 36: 435-40. 19 Esler M, Jennings G, Korner P, et al Total and organ specific noradrenaline plasma kinetics in essential hypertension. Clin Exp Hyper 1984; 86: 507-22. 20 Brown MJ, Jenner DA, Allison DJ, Dollery CT. Variations in individual organ release of noradrenaline measured by an improved radioenzymatic technique Clin Sci 1981, 61: 585-90. 1 American Psychiatric Association. DSM III Washington, DC: APA, 1980. 2. Trimble MR. Post-traumatic neurosis. Chichester: John Wiley, 1981
traumatic neurosis or accident neurosis. This condition, which costs individuals, governments, communities, and insurance companies vast sums in lost earnings or compensation payments, has curiously been the subject of very little research, although most physicians must have encountered patients in whom such symptoms have developed after accidents, often of a minor nature. The main arena where the condition is discussed is the medicolegal circus, in which it is customary to find two eminent physicians-one appearing for the plaintiff, the other for the defence-giving contradictory views not only about the status of the patient’s symptoms but also about their aetiology and pathogenesis. Many of the arguments relate to the question of malingering, and whether the patient is producing symptoms for personal financial gain. The author most often cited by those springing to the defence of insurance companies is the late Henry Miller, who was led to the conclusion that accident neurosis (the term he preferred) was "not the result of the accident but a concomitant of the compensation and the manifestation of the hope of financial gain".3 Thus it is confidently asserted that, once there has been a financial settlement, the patient will immediately return to work. Tarsh and Royston have now examined this question, after financial settlement, in 35 litigants, all of whom had severe somatic symptoms in the absence of clearly defined physical ills. In contrast to Miller’s cases, these
patients were referred by the plaintiffs’ solicitors. They were traced after a substantial amount of detective work and interviewed regarding their settlement and outcome. Amongst the conclusions of Tarsh and Royston, three are of special note. First, "return to work was the exception rather than the rule, and did not occur in two-thirds of those involved". This very clear finding substantiates the results of several other workers including Kellywho, as a conclusion to his own follow-up study, noted "it is not longer justifiable for a neurologist or lawyer to stand up in court and affirm that it is well known that patients with such symptoms immediately return to work after their claim has been settled". Mendelson,6 reviewing the published work in 1982, emphasised several other studies that substantiate this view, in contrast to the assertions of Miller. Secondly, working on a suggestion of Kelly5 that resentment was a common obstacle in such cases, they noted that claimants reserved most of their wrath for the medicolegal merry-go-round. In particular, patients were distressed by the number of different medical examinations that they had to attend, and the lack of any attempt at treatment. Thirdly, the development of behaviour patterns within the family after the accident seemed more important than any pre-existing personality disorder in contributing to the prolongation of symptoms. This matter, rarely discussed and never examined systematically, is clearly open for future research. In view of the increasing number of studies that emphasise the continuation of post-traumatic neurosis after settlement, it is a wonder that the alternative view, that they will soon recover, continues to be expressed. The designation of "posttraumatic stress disorder" by the American Psychiatric Association, and the growing body of published work, should stimulate clinicians to heed this syndrome so frequently neglected outside the high courts. 3 Miller H Accident 4 Tarsh
neurosis. Br Med J 1961, i: 919-25, 992-98. MJ, Royston C A follow-up study of accident neurosis. Br J Psychiatry 1985
146: 18-25 5. Kelly R The post-traumatic syndrome. Roy Soc Med 1981, 24: 242-44. 6. Mendelson G Not "cured by a verdict"—effect of legal settlement on compensation claimants Med J Aust 1982; ii: 132-34.