Volume 168 Issue 8

Severe cervical spinal cord injuries related to rugby union and league football in New South Wales, 1984-1996 Tai R Rotem, James S Lawson, Stephen F Wilson, Stella Engel, Sue B Rutkowski and Chris W Aisbett MJA 1998; 168: 379-381 For editorial comment see Yeo Correction note: This article was published online with a typographic error that was corrected on 15 June 1998: A P value of 0.06 was misprinted as 0.6. Jump to corrected par. Abstract - Introduction - Methods - Results - Discussion - Acknowledgement - References - Authors' details - - ©MJA1998 Abstract Objective: To determine the frequency and circumstances of serious cervical cord injuries associated with rugby union and league football in New South Wales. Design: Retrospective review of patients with rugby football-related cervical spinal cord injuries. Setting: The two central spinal units in NSW, from January 1984 to July 1996. Outcome measures: Admission to spinal units; injury resulting in permanent tetraplegia. Results: During the review period, 115 rugby football players (56 union and 59 league) were admitted to the spinal units because of cervical spinal cord injuries. 49 patients had resultant permanent neurological deficits (complete tetraplegia [quadriplegia]) -- 26 associated with rugby union and 23 with rugby league. Two patients died of injury sequelae within two weeks of admission. There was no significant change in the rate of football-related admissions to spinal units for either code. There was a small decline in the number (from 15 in 1984 to 1987 to 7 in 1992 to 1996) and incidence (from 1.2 to 0.5 per 10 000 participants) of patients with tetraplegia associated with rugby union. When this decline was tested as a trend over the years, it was found to be statistically significant (P = 0.06). No significant trend was found in the tetraplegia data associated with rugby league. Cervical spinal cord injuries leading to complete tetraplegia were most commonly associated with scrum-like plays in union and with tackles in league. Conclusion: Serious cervical spinal injuries associated with both codes of rugby continue to occur in NSW. Rugby football in its various forms is still an inherently dangerous game. Introduction Injury to the cervical spinal cord sustained while playing rugby union or league football has tragic personal consequences, with subsequent high demands on community resources.1 During the 1970s and early 1980s there was an approximately twofold increase in the incidence of such injuries in many countries,2-4 possibly because of the development of more powerful scrums and tackles (see Box for terms). In response, between 1984 and 1996, new rules were introduced intermittently, existing rules were more strictly enforced, and "safety" programs were offered -- these included exercises for strengthening players' neck muscles and the banning of players with long thin necks from taking dangerous positions, such as the front row of scrums. We report the findings of a survey of rugby union- and league-related cervical spinal cord injuries in New South Wales (NSW) for the period 1984 to 1996. Methods We retrospectively reviewed the medical records of all patients admitted to the two central spinal units in NSW (at the Royal North Shore Hospital and Prince Henry Hospital, Sydney) because of cervical spinal cord injuries associated with rugby union and rugby league football from January 1984 to December 1996. Patients transferred from outside NSW were excluded from the analysis. Almost all patients (more than 95%) with spinal injuries that occur in NSW are admitted to these two units. Additional information about the circumstances of the injuries, including eyewitness reports of the events leading to them, was obtained from the NSW Sporting Injuries Committee -- a statutory authority which administers an insurance scheme for people permanently injured while playing sports. We also estimated the number of participants in rugby union and league football in NSW per year in the review period, based on the Committee's data5 plus surveys of NSW schoolboy football participants.6 As some of these data were incomplete and there was some duplication, these estimates are broad approximations only. Statistical analysis The number of cervical spinal cord injury cases is small, so any statistical analysis necessarily lacks power. To develop valid conclusions from this study, we analysed cases of cervical spinal cord injuries according to: total number of admissions to the two spinal units; permanent neurological deficits (ie, complete tetraplegia); and trends during the review period. When there are large numbers of participants and the risk of cervical spinal cord injury to any particular player is very low over a short time period -- and the injury is permanent and will not allow a return to the game -- the number of injuries in each year is assumed to follow a Poisson distribution. In the absence of data on hours of playing football or training for football, we assumed that the total number of hours devoted to the game for each code and grade did not vary from year to year. The null hypothesis for each test we performed was that there was no change in aggregated risk of cervical spinal injury against the alternative that the risk had decreased. All tests were based on the null-hypothesis assumption that the best estimate of annual rate of injuries was the average rate of injuries. We then fitted a simple linear regression, of time, to a probability transformation of the injury data. The number of injuries for each year was converted to the probability of observing, at most, that number of injuries in a particular year. These values were then converted to their corresponding standard normal score. The tests were based only on the regression slopes, which were tested to see if they were negative. The critical level of significance for these tests was 0.1. All calculations were performed using Microsoft Excel. The function POISSON was used to calculate the cumulative probabilities; the function NORMINV was used to calculate the standard normal scores; the function LINEST was used to calculate the slope and its standard error; and the function TDIST (one-tailed 11 degrees of freedom) was used to obtain the significance of the results. The Random Number Generator was used in a small simulation study to confirm the size of the testing procedure. Results During the 13-year period of the review, 117 rugby football players (56 union and 59 league players, plus one "backyard" and one "touch" player) were admitted to the spinal units because of cervical spinal cord injuries. The injuries were associated with permanent neurological deficits which led to complete tetraplegia (quadriplegia) in 26 union and 23 league players and in both the "backyard" and the "touch" football players. (The touch and backyard football players were not included in this analysis because they were not playing according to official union or league rules [Table 1].) The 23 "unspecified" admissions shown in Table 1 could not be included in the formal analysis because the football code was omitted from their clinical records. Two patients died of pneumonia within 14 days of sustaining the cervical spinal cord injuries. The age range of the injured players from both codes was 15-37 years (median, 22 years); all were male. The number of patients admitted per year to the spinal units because of cervical spinal cord injuries varied widely: from one to nine per year for league and one to eight per year for union. The number of players who had permanent tetraplegia varied from none to five per year for league and none to six for union (Table 1). Incidence and trends There were about 106 000 participants in rugby league and about 31 000 in rugby union in NSW during each year of the review.5,6 Trends in rates of admissions and incidence of permanent neurological deficits per 10 000 participants are shown in Table 2. Using the data shown in Table 1, there was no decline in the number (and hence the rate) of admissions for union (P = 0.21) or league (P = 0.33) players. There was a small but significant decline for union in the number and hence the incidence (P = 0.06) of players with permanent neurological deficits, but no significant decline for league (P = 0.16). Type of play associated with severe cervical spinal cord injuries Although detailed self-reports and eyewitness accounts of the events surrounding the injuries were available for 43 of the 49 patients with complete tetraplegia, no consistent patterns of play or events could be identified other than that the injury occurred in scrum-like plays (scrums, mauls and rucks; n = 23) or tackles (n = 26). Repeatedly, eyewitnesses observed that a player was found paralysed on the ground, without an obvious causal explanation, while the general play moved on. This lack of a specific, out-of-the-ordinary event was supported by two video recordings of cervical spinal cord injuries that occurred during scrums. The injuries were most common in scrum-like plays in union and in tackles in league. The most common level of spinal cord damage was C4-5 (Table 3). Discussion Despite its limitations as a retrospective study (such as the use of records created for other purposes), the findings of this review are disturbing. While for union players there was a small reduction in both the number and incidence of those with permanent neurological deficits leading to tetraplegia, there were no such changes for league players. Nor were there any changes for either code in the number of players admitted or rates of admission to spinal units. While any fall in the number and incidence of permanent neurological deficits among union players is pleasing and may well be a consequence of rule changes and safety measures,7 the unchanged rate of admissions to spinal units suggests that such improvements may not be sustained. In those players admitted to spinal units who do not experience permanent neurological deficits, the injuries can be regarded as "near misses" (ie, possible damage to the vertebral column without spinal cord injury).7 While evacuation procedures for suspected cervical and other spinal cord injuries may vary, such "near misses" included in the admission rates offer a useful indicator of the risks of such injuries associated with rugby union and league football.8 Our observation that cervical spinal cord injuries are more common in scrum-like plays in union and tackles in league is similar to recent findings in New Zealand.7 However, there is insufficient information in this review and in the New Zealand7 and other reviews9 of rugby football-associated spinal cord injury upon which to base sound recommendations for detailed changes to the rules or other safety measures. These reviews confirm the obvious -- that both rugby union and league are inherently dangerous games. There appear to be several options: Maintain the status quo and accept that each year several union and league players in NSW (and elsewhere) will suffer cervical spinal cord injuries which will leave them permanently paralysed below the neck; For rugby union, change the rules so as to substantially reduce the number of scrum-like plays and change the organisation of the scrum; For rugby league, introduce changes to the rules aimed at substantially altering the nature of the tackle. Acknowledgement This study was conducted with a grant from the NSW Sporting Injuries Committee. Disclaimer of conflict of interest: Apart from providing access to their own case files, the NSW Sporting Injuries Committee was in no way involved with the collection or analysis of data and did not have the right to disapprove or influence the contents of the manuscript. References Yeo JD. Prevention of spinal cord injuries in an Australian study (NSW). Paraplegia 1993; 31: 759-763. Taylor TKF, Coolican MRJ. Spinal cord injuries in Australian footballers, 1960-1985. Med J Aust 1987; 147: 112-118. Silver JR. Injuries of the spine sustained during rugby. BMJ 1984; 288: 37-43. Silver JR, Stewart D. The prevention of spinal injuries in rugby football. Paraplegia 1994; 32: 442-453. NSW Sporting Injuries Scheme. Annual reports of the NSW Sporting Injuries Committee. Sydney 1984 to 1995. Sydney: NSW Sporting Injuries Committee, 1984-1995. Northern Sydney Area Health Service. NSW Youth Sports Injury Report. July 1997. Sydney: Northern Sydney Area Health Service, 1997. Armour KS, Clatworthy BJ, Bean AR, et al. Spinal injuries in New Zealand rugby and rugby league -- a twenty-year survey. N Z Med J 1997; 110: 462-465. Noakes T, Jakoet I. Spinal cord injuries in rugby union players: How much longer must we wait for proper epidemiological studies? BMJ 1995; 310: 1345-1346. Kew T, Noakes TD, Kettles AN, et al. A retrospective study of spinal cord injuries in Cape Province rugby players, 1963-1989. S Afr Med J 1991; 80: 127-133. (Received 18 Sep 1997, accepted 27 Jan 1998) Authors' details School of Health Services Management, Faculty of Medicine, University of NSW, Sydney, NSW. Tai R Rotem, BSocSci, Research Fellow; James S Lawson, MD, MHA, Professor; Chris W Aisbett, BSc, Visiting Fellow. Department of Aged Care and Rehabilitation, Royal North Shore Hospital, Sydney, NSW. Stephen F Wilson, MB BS, FAFRM(RACP), Senior Staff Specialist. Department of Rehabilitation, Prince Henry Hospital, Sydney, NSW. Stella Engel, DPRM, FAFRM(RACP), Director. Spinal Injuries Unit, Royal North Shore Hospital, Sydney, NSW. Sue B Rutkowski, MB BS, Director. Reprints will not be available from the authors. Correspondence: Professor J S Lawson, School of Health Services Management, Faculty of Medicine, University of NSW, Sydney, NSW 2052. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Tai R Rotem · James S Lawson · Stephen F Wilson · Stella Engel · Sue B Rutkowski · Chris W Aisbett

Panic disorder: coronary spasm as a basis for cardiac risk? Virginia M Mansour, Dominic J C Wilkinson, Garry L Jennings, Rosemary G Schwarz, Jane M Thompson and Murray D Esler For editorial comment see Freedman & Tennant Patients with panic disorder often complain of angina-like chest pain during panic attacks, but this is not usually considered life-threatening. We describe three patients with panic disorder and documented cardiac ischaemia during episodes of chest pain. In two, it progressed to myocardial infarction. As none had atherosclerosis evident at coronary angiography, the mechanism was presumed to be coronary artery spasm. These cases illustrate that pain typical of angina during panic attacks may have an organic cause. (MJA 1998: 168; 390-392) Introduction - Case records - Discussion - Acknowledgement - References - Authors' details - - ©MJA1998 Introduction Panic disorder is characterised by unpredictable and overwhelming feelings of fear accompanied by various symptoms of sympathetic nervous system arousal, such as sweating, palpitations, diarrhoea, and tremor.1 Often, angina-like chest pain is also present, but detailed cardiac "workup" in patients with panic disorder typically shows no abnormalities. Thus, although panic disorder is distressing and disabling, it has not been thought life-threatening. However, recent well conducted, prospective epidemiological studies show substantially increased risk of myocardial infarction and sudden death in patients with panic disorder (three- to six-fold increase).2,3 These patients sit at the crossroads of cardiology and neuropsychiatry, and provide a clinical model for investigation of the relationship between stress and heart disease. The mechanism by which cardiac risk is increased in panic disorder is not known, but has been thought to involve activation of the sympathetic nerves of the heart, predisposing to ventricular arrhythmias. We present three patients with panic disorder and chest pain whose cases suggest coronary artery spasm as a pos sible mechanism. Case records All three patients met the diagnostic criteria for panic disorder of the Diagnostic and statistical manual of mental disorders (4th edition),4 and all were non-smokers. Patient 1 A 34-year-old woman presented to a hospital casualty department in November 1996 with severe chest pain radiating to her left arm and shortness of breath after having taken cocaine. She also complained of palpitations, dizziness, tremor, and an overwhelming sense of doom and fear. She had taken cocaine occasionally over the previous two years without panic symptoms. An electrocardiogram (ECG) showed inferolateral ST-segment depression suggesting ischaemia. The pain eased with sublingual nitroglycerine and intramuscular morphine. A thallium exercise stress test two weeks later gave normal results. The patient presented again a month later with recurrent episodes of severe chest pain accompanying panic attack symptoms. She had stopped using cocaine after the first panic attack. An ECG taken during persisting pain again showed inferolateral ST-segment depression (Figure 1, below). Serum creatine kinase (CK) levels were normal. Coronary angiography during subsequent hospital admission (when the patient was free of pain) showed a normal coronary arterial tree (Figure 1). The patient was prescribed the selective serotonin reuptake inhibitor paroxetine (20 mg, increasing to 40 mg, daily), low dose aspirin (100 mg daily) and alprazolam (0.5 mg daily). Over two months' follow-up, panic attacks were less frequent, but chest pain recurred with each. After the addition of the slow calcium-channel blocker amlodipine (5 mg daily), her infrequent panic attacks were pain-free. Patient 2 A 42-year-old woman suffered anteroseptal infarction in November 1996 after exercise. Although she had no antecedent panic attack, she had a nine-year history of panic disorder, with panic attacks commonly associated with chest pain. She had been jogging as usual that morning without any symptoms, and presented later in the day with chest tightness and left-arm pain. A 12-lead ECG (Figure 2, below) showed anteroseptal ST-segment elevation consistent with acute myocardial infarction. Acute coronary angiography (Figure 2) showed total occlusion of the left anterior descending coronary artery in its mid portion. Treatment with balloon angioplasty and abciximab (an inhibitor of platelet aggregation) achieved complete recanalisation, and the pain resolved. No atherosclerosis was evident in the coronary arterial tree. Although a vasodilator was not given during angiography, the treating cardiologist described the angiogram as indicating development of fresh thrombus at a site of spasm in an otherwise normal coronary artery. Low dose aspirin and amlodipine (5 mg daily) were prescribed. The patient had further panic attacks (without chest pain) until paroxetine (20 mg daily) was also prescribed. Patient 3 A 46-year-old man presented to a casualty department in October 1996 with severe chest pain during a panic attack. He had long-standing panic disorder and a 15-year history of mild essential hypertension treated by propranolol (40 mg daily). His ECG was normal in the casualty department, and he was not admitted. The chest pain failed to resolve over the next 10 hours and he attended his family doctor, who found a raised serum CK level and arranged urgent hospital admission. His serum CK level rose progressively in hospital, peaking at 518 U/L (normal range [NR], 0-130 U/L), with CK MB isoenzyme level 66 U/L (NR, 0-10 U/L), leading to a diagnosis of myocardial infarction. Coronary angiography 14 days later, when the patient was free of pain, gave normal results, with no evidence of atherosclerosis. Over the ensuing eight months, the patient had increasingly frequent panic attacks accompanied by angina-like pain. He was prescribed paroxetine (20 mg, increasing to 40 mg, daily) and alprazolam (0.5 mg daily). Although the panic attacks became less frequent when the daily paroxetine dose was increased to 40 mg, chest pain persisted until amlodipine (5 mg daily) and aspirin (100 mg daily) were added to the regimen. Discussion These three patients with panic disorder had otherwise inexplicable episodes of cardiac ischaemia. In all three, the panic attacks were typically accompanied by chest pain. In two, the documented ischaemic events (angina with ST-segment depression in one and myocardial infarction in the other) occurred during a panic attack. In the third, while myocardial infarction was associated with exercise rather than a panic attack, there was a long prior history of panic attacks with chest pain. None of the three had atherosclerosis evident on coronary angiography, and two were women with no classical cardiac risk factors. Coronary artery spasm was thought to be the underlying mechanism of the ischaemia in all three cases. In some circumstances, patients with primary cardiac arrhythmias can be misdiagnosed as having panic disorder.5 Similarly, it might perhaps be argued that our patients had variant angina, with the anxiety disorder developing after a period of misdiagnosis of the cause of the chest pain, so that the myocardial ischaemia was a cause rather than a consequence of the panic disorder. However, in Patients 2 and 3 the diagnosis of panic disorder antedated the development of chest pain during panic attacks, while in Patient 1 angina-like pain was a feature of the first and of most subsequent panic attacks. The mechanism by which coronary spasm develops in panic disorder is not clear. Cigarette smoking can underlie coronary spasm, but our three patients were non-smokers. Hyperventilation, often a concomitant of a panic attack, can precipitate coronary spasm in the presence of atheroma6 and even in coronary arteries free of atherosclerosis.7 Patients who had spontaneous panic attacks in the research laboratory have shown a substantial increase in adrenaline secretion and sympathetic nervous system activity. 8 However, adrenaline typically increases, rather than decreases, coronary blood flow by means of b -adrenergic coronary vasodilatation.9 Similarly, sympathetic nervous system stimulation usually causes coronary vasodilatation and increases flow, partly through the attendant metabolic myocardial stimulation, but also through direct effects on the vasculature.9 In some circumstances, disorders of coronary vasomotion have been linked to dysfunction of the vascular endothelium. Endothelial function was not assessed in our patients, but such tests would be relevant for future prospective studies given that the mechanism of presumed spasm remains elusive. We suspect that coronary spasm is not uncommon during panic attacks, particularly in patients with typical angina-like pain, and that panic disorder may be an undetected cause of otherwise inexplicable coronary heart disease, especially in premenopausal women, who are otherwise at low cardiac risk. It may possibly overlap clinically with "Syndrome X", a poorly understood condition in which recurrent myocardial ischaemia occurs despite the presence of structurally normal coronary arteries. This condition, not to be confused with the endocrinological Syndrome X (insulin metabolic resistance syndrome),11 seems to result, not from coronary spasm, but from reduced myocardial flow reserve caused by a functional abnormality in the cardiac microcirculation.10 Formal testing involving measurements of coronary blood flow under conditions which increase it reflexly, such as exercise, would be needed to exclude this syndrome. An understanding of the mechanism of coronary spasm in panic disorder would facilitate therapeutic intervention. At present, we treat patients with panic disorder and clinical evidence of coronary spasm with drugs and other measures aimed at preventing or minimising their panic attacks,1 a slow calcium-channel blocker as a non-specific antispasm measure, and low dose aspirin as prophylaxis against coronary thrombosis during spasm. It is difficult to know how far to pursue cardiac testing in patients with panic disorder. As we believe their level of cardiac risk is low overall, we recommend selective investigation of those with typical angina-like pain during panic attacks. Capturing ECG evidence of myocardial ischaemia during a panic attack, either during clinic or emergency department attendance or on Holter monitoring, is of central clinical relevance. While it is important to exclude the presence of fixed coronary artery stenosis (which may coexist, particularly in older patients), standard provocative ischaemia testing is not entirely satisfactory; exercise or vasodilator pharmacological challenges are inappropriate for behaviourally induced ischaemia. Panic attacks can be induced in some patients by breathing a mixture of carbon dioxide (10%-15%) and oxygen.12 ECG or thallium stress testing using this stimulus as a challenge is worth future research evaluation. Panic disorder may provide a useful clinical model for studying the possible link between stress and heart disease. A direct relationship between mental stress and sudden death has been seen in special circumstances, such as inherited long-QT-interval syndromes, in which there is electrical instability of the heart muscle.13 In addition, rates of non-traumatic sudden death were markedly increased in people with underlying coronary disease during the 1994 Los Angeles earthquake.14 However, research on stress and heart disease has been hampered by disagreement over what constitutes stress and how to measure it. In panic disorder, the episodes of recurring, often inexplicable, anxiety can be regarded as repeated mental stress reactions. The study of cardiac risk during panic attacks may be a valid method for testing the general proposition that the clinical endpoints of ischaemic heart disease can be "triggered" by stressful events. Acknowledgement This work was supported by a Project Grant from the National Heart Foundation of Australia and an Institute Grant to the Baker Medical Research Institute from the National Health and Medical Research Council of Australia. The contributions of Dr David Prior and Sister Leonie Johnston in the research cardiac catheter laboratory are gratefully acknowledged. The authors also wish to thank Dr Emmanuel G Manolas for provision, through the Epworth Hospital, of clinical and angiographic findings on his patient. References Agras WS. The diagnosis and treatment of panic disorder. Annu Rev Med 1993; 44: 39-51. Kawachi I, Colditz GA, Ascherio A, et al. Prospective study of phobic anxiety and risk of coronary heart disease in men. Circulation 1994; 89: 1992-1997. Kawachi I, Sparrow D, Vokonas PS, Weiss ST. Symptoms of anxiety and risk of coronary heart disease. Circulation 1994; 90: 2225-2229. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994: 394-403. Lessmeier TJ, Gamperling D, Johnson-Liddon V, et al. Unrecognized paroxysmal supraventricular tachycardia. Potential for misdiagnosis as panic disorder. Arch Intern Med 1997; 157: 537-543. Girotti LA, Crosatto JR, Messuti H, et al. The hyperventilation test as a method for developing successful therapy in Prinzmetal angina. Am J Cardiol 1982; 49: 834-841. Yasue H, Nagao M, Omote S, et al. Coronary arterial spasm and Prinzmetal's variant form of angina induced by hyperventilation and Tris-buffer infusion. Circulation 1978; 58: 56-62. Wilkinson DJC, Thompson JM, Lambert GW, et al. Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress and during panic attacks. Arch Gen Psychiatry 1998. In press. Hjemdahl P. Physiology of the autonomic nervous system as related to cardio vascular function: implications for stress research. In: Byrne DG, Rosenman RH, editors. Anxiety and the heart. New York: Hemisphere Publishing, 1990: 95-158. Fragasso G, Rossetti E, Dosio F, et al. High prevalence of the thallium-201 reverse redistribution phenomenon in patients with Syndrome X. Eur Heart J 1996; 17: 1482-1461. Alford FP. Syndrome X (insulin resistance metabolic syndrome): a deadly quartet or an awesome foursome? Med J Aust 1996; 164: 4-5. Battaglia M, Perna G. The 35% CO 2 challenge in panic disorder: optimization by receiver operating characteristics (ROC) analysis. J Psychiatr Res 1995; 29: 111-119. Zipes DP. The long QT interval syndrome. A rosetta stone for sympathetically mediated ventricular tachyarrhythmias. Circulation 1991; 84: 1414-1419. Leor J, Poole WK, Kloner RA. Sudden cardiac death triggered by an earthquake. N Engl J Med 1996; 334: 413-419. (Received 28 Aug 1997, accepted 21 Jan 1998) Authors' details Baker Medical Research Institute, Melbourne, VIC. Virginia M Mansour, MB BS, Clinical Research Associate; Jane M Thompson, MB BS, Clinical Research Associate; Murray D Esler, PhD, FRACP, Associate Director. Melbourne University, Melbourne, VIC. Dominic J C Wilkinson, BMedSci, Medical Student. Alfred Hospital Heart Centre, Melbourne, VIC. Garry L Jennings, MD, FRACP, Director. Medical Advisory Committee, The Melbourne Clinic, Melbourne, VIC. Rosemary G Schwarz, FRANZCP, Chair. Reprints: Professor M D Esler, Human Neurotransmitter Research Laboratory, Baker Medical Research Institute, PO Box 348, Prahran, VIC 3181. E-mail: Esler AT Baker.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Virginia M Mansour · Garry L Jennings · Rosemary G Schwarz · Jane M Thompson · Murray D Esler