Volume 187 Issue 6

Potentially serious metabolic sequelae make diagnosis and intervention imperatives Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality of women of reproductive age. The diagnosis is based on the presence of two of three criteria — ovulatory disturbance, hyperandrogenism, and polycystic ovaries on ultrasound. However, in most women, insulin resistance is central to the pathogenesis of the syndrome, with hyperinsulinaemia driving both androgen production and androgen bioavailability as the key diagnostic feature.1-3 In PCOS, insulin resistance not only contributes to symptoms, but also has serious sequelae including infertility, impaired glucose tolerance, a fourfold to sevenfold increase in diabetes and a potentially increased risk of cardiovascular disease.3 PCOS affects an estimated 400 000 Australian women; this is 5%–10% of the reproductive age group. Obesity exacerbates insulin resistance and glucose intolerance in PCOS. As obesity in the community increases, the prevalence of the PCOS phenotype and its associated glucose intolerance — including diabetes — are expected to rise significantly. In 2006, the estimated economic burden of PCOS in the United States was $6 billion, equating to $400 million in health care costs in Australia (with menstrual dysfunction consuming 31%, infertility 12% and PCOS-associated diabetes 40% of total costs), representing a major health and economic burden.4 An economic evaluation of PCOS recently advocated screening, diagnosis and intervention, justifiable by ameliorating or preventing serious sequelae.4 However, greater understanding of appropriate screening, long-term risks and effective interventions is urgently needed. In this issue of the Journal, Dabadghao and colleagues report a retrospective study of a large cohort of Australian women with PCOS presenting to an infertility service, and tackle the important issues of abnormal glucose tolerance and metabolic syndrome in PCOS (→ Glucose tolerance abnormalities in Australian women with polycystic ovary syndrome).5 In the study by Dabadghao et al, most women with PCOS were obese, with a mean body mass index (BMI) in their cohort of 35 kg/m2. Impaired glucose tolerance was noted in 15.6% and diabetes in 4%.5 The key predictors of abnormalities in glucose tolerance were age, BMI, metabolic syndrome and a family history of diabetes.5 Previous reports on the prevalence of metabolic complications of PCOS have shown inconsistent results, related to the diversity of populations studied (age, BMI, ethnicity) and the different diagnostic criteria applied for PCOS and for impaired glucose tolerance and diabetes. The study by Dabadghao et al used the current Rotterdam criteria for diagnosing PCOS and the World Health Organization criteria for impaired glucose tolerance and diabetes. While the ethnicity of the population is not described in the Dabadghao et al study, and the population is selected (all women had attended a fertility service), their findings in this large cohort highlight the high prevalence of metabolic complications in women with PCOS in Australia. PCOS is a heterogeneous condition, and there are undoubtedly varied genetic and environmental influences on its development and expression, with challenging clinical and research questions still to be answered. However, given the aetiological and exacerbating roles of obesity and insulin resistance in most women with PCOS, it is imperative that clinicians are aware of the metabolic implications of this syndrome. Screening for metabolic complications, as recommended by Dabadghao et al, needs to include a 75 g 2-hour oral glucose tolerance test and lipid profile determination at diagnosis, and regularly over time.5,6 Frequency of screening should be based on the key predictors for development of diabetes (as noted by Dabadghao et al) — age, BMI and family history of diabetes.5 It should be noted that measuring insulin levels does not have a clinical role in screening or in guiding management and remains a research tool. Prevention and treatment strategies should also be more aggressively pursued in these higher risk subgroups. Lifestyle modifications are first-line interventions in the treatment of insulin-resistance states (obesity, PCOS, prediabetes and diabetes). In PCOS, improvements in insulin resistance, ovulation, androgen levels and fertility have been shown with as little as a 4%–5% drop in bodyweight achieved with caloric restriction (independent of dietary composition), with or without exercise programs.7,8 In populations not affected by PCOS, lifestyle changes as well as insulin sensitisers (including metformin) significantly delay the onset of diabetes in those with impaired glucose tolerance;9 similar delay is likely with such changes in patients with PCOS. Lifestyle therapy should be realistic (initial goal of about 5% weight loss), feasible, achieved through sustainable lifestyle change rather than short-term caloric restriction, and supported by a multidisciplinary approach.7,8 In combination with lifestyle change, insulin sensitisers are likely to have a role in those at highest risk, especially where impaired fasting glucose or impaired glucose tolerance is already established.10-12 It is now recognised that PCOS is not simply a reproductive condition characterised by the appearance of the ovary on ultrasound, but represents a complex interplay between insulin metabolism and androgen production. The high prevalence of abnormalities of glucose metabolism and of the metabolic syndrome in women with PCOS mandates a proactive approach to screening and prevention. A recent survey of Australian clinicians treating women with PCOS found that screening for metabolic complications of PCOS has not been as widely practised as is advocated and supported by the literature in general,13 including the study by Dabadghao et al. A change to more proactive screening and intervention is likely to reduce the burden of disease associated with PCOS.

Helena J Teede FRACP, PhD · Bronwyn G A Stuckey BA, FRACP

Combining clinical diagnostic scoring with D-dimer analysis Venous thromboembolism (VTE) occurs in one to two people per 1000 annually in Caucasian populations.1 About a third of these patients will have symptomatic pulmonary embolism (PE), which is associated with a mortality rate of about 30% if left untreated.2 Anticoagulant therapy is highly effective for preventing death in patients with symptomatic PE,3 but causes major bleeding in 2% of patients during the first 3 months. The mortality rate among patients who suffer major bleeding is about 10%.4 Accurate diagnosis is thus critical to ensure that patients with PE receive effective treatment and that patients without PE do not receive unnecessary anticoagulant therapy, with its associated risks and inconvenience. The diagnosis of PE is challenging because of the wide spectrum of symptoms and signs, and because most patients with suggestive clinical features do not have the disease.5,6 Major risk factors for PE include trauma, surgery, and a diagnosis of cancer, but half of patients with symptomatic PE do not have an identifiable risk factor.1 Typical symptoms of PE include dyspnoea or acute chest pain and, less commonly, cough or haemoptysis, while typical signs include tachycardia, tachypnoea and, less commonly, right ventricular dysfunction.5 However, none of the typical clinical symptoms and signs are unique to the disorder or invariably present in patients with confirmed PE. Thus, the clinical diagnosis of PE is unreliable and additional testing is required to confirm or refute the diagnosis. The accuracy of non-invasive testing, which has almost completely replaced pulmonary angiography in the diagnosis of PE, is substantially improved when combined with an assessment of clinical pre-test probability and the results of a sensitive D-dimer assay.5 Experienced clinicians can use clinical judgment (“gestalt”) to assign a pre-test probability of PE with reasonable accuracy, but simple clinical prediction rules, such as the one developed by Wells and colleagues,7 perform equally well and can be used by less experienced clinicians.5 To date, the Wells model has not been evaluated in an Australian setting. In this issue of the Journal, Yap and colleagues report the results of a prospective cohort study in which they evaluated the use of Wells’ model in 633 consecutive inpatients and outpatients with suspected PE referred for lung scanning at a major Australian teaching hospital (→ A prospective reassessment of the utility of the Wells score in identifying pulmonary embolism).8 Lung scans and multidetector computed tomography (MDCT) were used as the reference standard to establish the diagnosis of PE (positive lung scan or positive MDCT) or to exclude PE (negative lung scan or non-diagnostic scan with negative MDCT). They found that a low clinical pre-test probability of PE (Wells score < 2) was associated with a 4.3% prevalence of PE; a moderate clinical pre-test probability of PE (Wells score 2–6) was associated with a 13% prevalence of PE; and a high clinical pre-test probability of PE (Wells score > 6) was associated with a 67% prevalence of PE. There was no follow-up of patients once diagnostic imaging was completed, and PE may have remained undiagnosed in some patients. Nonetheless, the prevalence of PE in the low, moderate and high pre-test probability categories reported by Yap and colleagues is almost identical to the prevalence reported in the original study by Wells and colleagues,7 and confirms the ability of the Wells score to accurately classify patients according to their clinical pre-test probability of PE. Some investigators9,10 have suggested that patients with a low pre-test probability of PE do not require further investigation because the prevalence of disease in this group is low. However, the risk of missing a diagnosis of PE in such patients can be further minimised by combining the clinical assessment of pre-test probability with the results of a D-dimer assay. Depending on the sensitivity of the D-dimer assay, patients with low or moderate pre-test probability for PE may not require diagnostic imaging if they have a negative D-dimer test. Patients with a low pre-test probability and a negative moderately sensitive D-dimer assay, or patients with a low or moderate pre-test probability and a negative highly sensitive D-dimer assay do not require diagnostic imaging because the prevalence of disease in these patients is very low (less than 2%).11 By contrast, patients with a positive D-dimer test and/or those with a high pre-test probability require diagnostic imaging. For the past 20 years, clinicians have used lung scanning as the first-line non-invasive imaging test for patients with suspected PE. A normal or near-normal lung scan reliably excludes PE, while a high-probability lung scan confirms the diagnosis. However, as many as half of patients with suspected PE have a non-diagnostic lung scan result, and a quarter of these have PE.12 Newer lung scanning techniques may reduce the proportion of non-diagnostic scans, although the number of non-diagnostic scans reported by Yap and colleagues is unexpectedly low. MDCT is more rapid and convenient than lung scanning, but requires intravenous injection of contrast medium that is potentially nephrotoxic. The test can also yield non-diagnostic results.13 Clinicians must interpret non-diagnostic results of imaging studies in the context of the clinical pre-test probability of PE: patients with a moderate or high pre-test probability of PE and a non-diagnostic scan generally require additional or serial testing to establish or refute the diagnosis.12,13 Patients for whom there is a marked discrepancy between the pre-test probability of PE and the results of diagnostic imaging should also undergo further testing.13 The outcomes for patients with suspected PE can be improved by routine use of written diagnostic algorithms that incorporate a clinical probability scoring system.14 Yap and colleagues have validated the Wells probability scoring system in the Australian setting, and their data should encourage efforts by clinicians and institutions to implement standardised diagnostic strategies that combine assessment of clinical probability with measurement of a sensitive D-dimer in all patients with suspected PE.

Simon J McRae MB BS, FRACP, FRCPA · John W Eikelboom MB BS, MSc, FRACP

Objectives: To determine the prevalence of glucose tolerance abnormalities and to identify associated risk factors in women with polycystic ovary syndrome (PCOS) attending a reproductive endocrinology clinic.Design: Retrospective chart review.Participants and setting: 372 women with confirmed PCOS attending a reproductive endocrinology clinic at Adelaide University’s Research Centre for Reproductive Health.Main outcome measures: Prevalence of glucose tolerance abnormalities and association of such abnormalities with potential risk factors.Results: 4.0% (15 women) had diabetes mellitus, 15.6% (58) had impaired glucose tolerance and 80.4% (299) had normal glucose tolerance. There was a significant trend towards increasing prevalence of diabetes with increasing age (odds ratio [OR], 0.60; P = 0.0085). The prevalence of abnormal glucose tolerance (diabetes and impaired glucose tolerance together) was significantly higher with higher waist circumference (OR, 2.9; P = 0.05), higher body mass index (OR, 8.02; P = 0.0253), a family history of diabetes (OR, 1.56; P = 0.0192) and the presence of metabolic syndrome (OR, 5.62; P < 0.001).Conclusion: The prevalence of diabetes and impaired glucose tolerance is high in women with PCOS, especially in older women and those with abdominal obesity and a family history of diabetes.

Preeti Dabadghao MD · Bronwen J Roberts RN · Jim Wang PhD · Michael J Davies BA(Hons), MPH, PhD · Robert J Norman MD, FRACOG, CREI

Objective: Design, setting and participants: Prospective, consecutive series of 633 studies on 595 patients referred to a major teaching hospital for ventilation/perfusion (V/Q) scanning for suspected acute PE between September 2004 and November 2005. Ventilation scintigraphy was performed using technetium-99m Technegas, and V/Q results were interpreted in conjunction with Wells scores.Main outcome measures: Likelihood of PE for each Wells score interval; overall prevalence of PE.Results: The likelihood of PE for a given Wells score in our study was not significantly different from the likelihood in the original study by Wells et al. Scores of < 2 in our study were associated with a 4% risk of PE, scores between 2 and 6 with a 13% risk, and scores > 6 with a 67% risk. The overall prevalence of PE in our study was significantly less than that in the original study (9% v 16%; P < 0.01), attributable to a significantly larger proportion of our patients having scores of < 2 (66% v 40%; P < 0.0001).Conclusion: The Wells score remains a robust clinical tool for stratifying the likelihood of PE. Patients with Wells scores of > 2 warrant imaging assessment for PE, but for those with scores < 2, further imaging may be problematic.

Kenneth S K Yap MB BS, FRACP · Victor Kalff MB BS, FRACP, FACC · Alla Turlakow MB BS, FRACP · Michael J Kelly MB BS, FRACP

Objective: To investigate the effectiveness and safety of acupuncture in persistent allergic rhinitis (PAR)Design: Randomised, single-blind, sham-controlled trial conducted from May 2004 to February 2005.Participants and intervention: 80 patients with PAR (age, 16–70 years) were randomly assigned to receive real or sham acupuncture. After a 1-week baseline period, participants were treated twice weekly for 8 weeks and followed up for another 12 weeks.Main outcome measures: Nasal obstruction, sneezing, rhinorrhoea and nasal itch were each self-assessed daily on a 5-point scale, and scores were aggregated weekly. The sum of the symptom scores (total nasal symptom score, TNSS) was also determined. A secondary outcome was use of PAR relief medication.Results: After 8 weeks’ treatment, the weekly mean difference in TNSS from baseline was greater with real (−17.2; 95% CI, −24.6 to −9.8) than with sham acupuncture (−4.2; 95% CI, −11.0 to 2.7) (P = 0.01). The decrease in individual symptom score was also greater with real acupuncture for rhinorrhoea (P < 0.01) but not the other symptoms. At the end of follow-up, the greater difference in TNSS from baseline in the real acupuncture group was still apparent: real, −21.0 (95% CI, −29.1 to −12.9) versus sham, − 2.3 (95% CI, −10.2 to 5.6) (P = 0.001). Moreover, the differences from baseline in all four individual symptom scores were greater for the real than for the sham group (P < 0.05). Real and sham acupuncture were both well tolerated.Conclusion: Our findings suggest that acupuncture is effective in the symptomatic treatment of PAR.Trial registration: Australian Government Therapeutic Goods Administration CTN 034/2004.

Charlie C L Xue BMed, PhD · Xuedong An BMed, MApplSc · Thomas P Cheung MSc · Cliff Da Costa PhD · George B Lenon PhD · Frank C Thien MD · David F Story PhD

Objective: To audit the clinical indications for HFE gene mutation testing in a consecutive series of requests.Design: Retrospective audit of reasons prompting 187 HFE test requests received between June 2003 and June 2005, by examination of the request form, hospital notes (when available) and, when required, information from the referring doctor.Setting: A tertiary care public teaching hospital laboratory, Perth, Western Australia.Main outcome measures: Reasons prompting requests for HFE genotype testing and compliance with accepted clinical indications (biochemical evidence of iron overload on repeated samples, or a first-degree relative with either haemochromatosis or a C282Y mutation).Results: Insufficient clinical details in requests prevented the inclusion of interpretive comments in HFE genotype reports in 70 of 187 cases (37%). Re-evaluation after collation of the missing details for all but seven requests revealed that 103 of the 180 auditable requests (57%) had been prompted for reasons other than biochemical evidence of iron accumulation or family history.Conclusions: A substantial proportion of HFE genotype test requests are made for inappropriate reasons. Clinical practice could be improved by educating doctors on the practical utility of this genetic test and by laboratories taking steps to secure the clinical information needed to include appropriate interpretive comments in their reports.

Melissa J Gillett FRCPA, FRACP · Cyril D Mamotte PhD · David Ravine MD, FRACP, FRCPA · Samuel D Vasikaran MD, FRCPA

Three cases of cholera in women aged 71, 72 and 84 years were notified in November 2006 in Sydney, New South Wales. This is the first reported cluster of cholera in Australia for over 30 years, and was an unusual outbreak in patients with no history of recent travel to cholera-endemic areas. A food trace-back investigation found that the only exposure common to all cases was consumption of raw whitebait imported from Indonesia. This outbreak demonstrates that the practice of eating raw whitebait does occur in Australia, albeit in the process of taste-testing uncooked fritter batter. All three patients were undergoing long-term therapy with proton-pump inhibitors, which may have contributed to their susceptibility to the disease. A review of importation practices of food from cholera-endemic regions may be required to prevent future transmission.

Bradley Forssman MB BS, MPHTM, FAFPHM · Trish Mannes BAppSci, MPH · Jennie Musto MPH · Thomas Gottlieb MB BS, FRACP, FRCPA · Graham Robertson MSc · Jonathan D Natoli BSc · Craig Shadbolt PhD · Brian Biffin · Leena Gupta MB BS, MPH, FAFPHM

Objectives: To investigate the correlation between the publication “track record” score of applicants for National Health and Medical Research Council (NHMRC) project grants and bibliometric measures of the same publication output; and to compare the publication outputs of recipients of NHMRC program grants with those of recipients under other NHMRC grant schemes.Design: For a 15% random sample of 2000 and 2001 project grant applications, applicants’ publication track record scores (assigned by grant assessors) were compared with bibliometric data relating to publications issued in the previous 6 years. Bibliometric measures included total publications, total citations, and citations per publication. The program grants scheme underwent a major revision in 2001 to better support broadly based collaborative research programs. For all successful 2001 and 2002 program grant applications, a citation analysis was undertaken, and the results were compared with citation data on NHMRC grant recipients from other funding schemes.Main outcome measure: Correlation between publication track record scores and bibliometric indicators.Results: The correlation between mean project-grant track record scores and all bibliometric indicators was poor and below statistically significant levels. Recipients of program grants had a strong citation record compared with recipients under other NHMRC funding schemes.Conclusion: The poor correlation between track record scores and bibliometric measures for project grant applications suggests that factors other than publication history may influence the assignment of track record scores.

Marcus B Nicol BSc, MPH, PhD · Kumara Henadeera PhD · Linda Butler BEcon

Aboriginal and Torres Strait Islander people are three times more likely than non-Indigenous Australians to report vision loss due to cataracts, but are four times less likely to have cataract surgery. To increase access for Aboriginal and Torres Strait Islander people to cataract surgery, we need to identify the barriers to current services and trial strategies to overcome these barriers. Barriers to cataract surgery exist at the health service, community and individual level. Health service factors include infrastructure, cost, and provision of interpreters, escorts and transport. Community factors include social support, perceptions about the success of surgery, and beliefs about the causes of cataracts. Individual factors include ignorance that cataracts can be cured, fear of surgery or poor outcome, and comorbidity. Strategies proven to increase uptake of cataract surgery in other countries could be trialled in remote Australia.

Susan M Wearne

Tako-tsubo cardiomyopathy (TTC) is an important differential diagnosis of acute coronary occlusive myocardial infarction that should be understood by all clinicians. Although TTC is frequently clinically indistinguishable from acute left anterior descending coronary artery occlusion, it is readily differentiated with coronary angiography. The increasing frequency of acute angiography and revascularisation for patients with acute myocardial infarction has resulted in TTC being far more frequently diagnosed. Most common in postmenopausal women, TTC is frequently precipitated by physical or emotional stress, and after an acute phase during which the patient may be significantly haemodynamically compromised, there is rapid recovery and an excellent prognosis. After diagnosis the patient can be reassured and advised of the low rates of recurrence. Currently, no specific preventive therapy has been proven to be effective.

Irfan Abdulla BSc · Michael R Ward MB BS, FRACP, PhD

Excess serotonin in the central nervous system leads to a condition commonly referred to as the serotonin syndrome, but better described as a spectrum of toxicity — serotonin toxicity. Serotonin toxicity is characterised by neuromuscular excitation (clonus, hyperreflexia, myoclonus, rigidity), autonomic stimulation (hyperthermia, tachycardia, diaphoresis, tremor, flushing) and changed mental state (anxiety, agitation, confusion). Serotonin toxicity can be: mild (serotonergic features that may or may not concern the patient); moderate (toxicity which causes significant distress and deserves treatment, but is not life-threatening); or severe (a medical emergency characterised by rapid onset of severe hyperthermia, muscle rigidity and multiple organ failure). Diagnosis of serotonin toxicity is often made on the basis of the presence of at least three of Sternbach’s 10 clinical features. However, these features have very low specificity. The Hunter Serotonin Toxicity Criteria use a smaller, more specific set of clinical features for diagnosis, including clonus, which has been found to be more specific to serotonin toxicity. There are several drug mechanisms that cause excess serotonin, but severe serotonin toxicity only occurs with combinations of drugs acting at different sites, most commonly including a monoamine oxidase inhibitor and a serotonin reuptake inhibitor. Less severe toxicity occurs with other combinations, overdoses and even single-drug therapy in susceptible individuals. Treatment should focus on cessation of the serotonergic medication and supportive care. Some antiserotonergic agents have been used in clinical practice, but the preferred agent, dose and indications are not well defined.

Geoffrey K Isbister MB BS, MD, FACEM · Nicholas A Buckley BMed, MD, FRACP · Ian M Whyte MB BS, FRACP

A woman in her 20s presented to the emergency department, malnourished and dehydrated, and with acute paralysis of the lower limbs. Over the previous 10 days, she had inhaled nitrous oxide from “whipped-cream bulbs” (10–20 per day) for pain caused by a sprained ankle. She had a history of intravenous drug use and was on a methadone program. The nitrous oxide misuse combined with the malnutrition, with low vitamin B12 levels, apparently resulted in subacute combined degeneration of the spinal cord — a rare complication of nitrous oxide misuse. Clinical recordA young woman in her 20s presented to the emergency department with a history of increasing difficulty in mobilising over the previous week. For the 3 days before presentation, she had been confined to the back seat of a car (from which she was extricated with difficulty on arrival at the emergency department). An estimated 60 empty “whipped-cream bulbs” were found on the floor of the car. She had a history of intravenous drug use and was on a methadone program, but there was no other significant medical history. She had sprained her ankle 10 days before presentation, and had been inhaling nitrous oxide from whipped-cream bulbs for the pain (10–20 per day). Further immobility and boredom had increased her usage. On examination, she was pleasant, but dishevelled and malnourished, with evidence of needle track marks from intravenous drug use on her extremities. She had a Glasgow Coma Scale score of 14/15 (best eye response, 4; best verbal response, 4; best motor response, 6); her respiratory rate was 20 breaths/min; heart rate, 95 beats/min; blood pressure, 95/63 mmHg; temperature, 35.6°C; and oxygen saturation in room air was 94%. She had a 1/5 flaccid proximal weakness of the lower limbs (Medical Research Council [United Kingdom] scale), with a flicker of power preserved distally, but absent plantar and knee-jerk reflexes. She had a patchy sensory level to T10, and absent vibration sense to her anterior superior iliac spines bilaterally. There was a proprioception deficit to her feet, knees and hips bilaterally. She was in urinary retention, and 1800 mL was drained through an indwelling urinary catheter. Rectal examination showed atony of the anal sphincter. There were mild pressure areas on the dorsal surfaces of her legs and buttocks, with diffuse oedema of the lower limbs. The rest of the examination was unremarkable. InvestigationsDifferential diagnoses included a space-occupying lesion of the spinal cord, transverse myelitis, HIV myelopathy, Guillain–Barré syndrome, and multiple sclerosis. We were concerned about the presence of a neurological toxin in the whipped-cream bulbs, given the history of neurological deterioration coinciding with the patient’s excessive use of the bulbs. Our diagnosis was initially delayed, as we were unable to ascertain the exact constituents of a whipped-cream bulb. Magnetic resonance imaging (MRI) of the whole spine and brain was performed and was initially reported as showing no abnormality. Initial laboratory investigations showed: a raised serum creatine kinase level of 9000 U/L (reference range [RR], < 150 U/L); acute renal failure, with a creatinine level of 490 μmol/L (RR, 80–140 μmol/L) and a urea level of 41 mmol/L (RR, 2.5–7.5 mmol/L); a troponin leak of 0.7 μg/L (RR, < 0.05 μg/L); and a normocytic anaemia, with a haemoglobin level of 83 g/L (RR, 120–140 g/L) and a mean cell volume of 95 fL. Vitamin B12 levels were 124 pmol/L (RR, > 210 pmol/L). A lumbar puncture was attempted but, on sitting the patient upright, she had a bradycardiac arrest and required cardiopulmonary resuscitation (CPR) for 30 s, resulting in spontaneous return to circulation and heart rate. Her arrested circulation was most likely the result of her being dehydrated (as evidenced by prerenal renal failure). Given her clinically demonstrated neuropathy, it is possible that a combination of autonomic neuropathy and reduced intravascular volume from dehydration, together with orthostatic stress on positioning, resulted in the precipitous fall in blood pressure, bradycardia, and arrest. This would explain the rapid return to cardiac output on return to a supine position, with only transient CPR. A Doppler ultrasound scan of the lower limbs showed bilateral deep venous thrombosis (DVT) to the level of the common femoral arteries. Indirect evidence of pulmonary embolus (PE) included a large alveolar–arterial gradient of > 100 mmHg (RR, 10–25 mmHg) and electrocardiogram changes — tachycardia and a right bundle branch block. It was decided not to perform a computed tomography pulmonary angiography, given the strongly supportive evidence for PE, and an intravenous contrast load was contraindicated given her acute renal failure. A further PE on upright positioning may also have contributed to her cardiac arrest; however, her rapid return to baseline clinical status on returning to a supine position does not support this. Clinical courseThe patient was resuscitated in the emergency department, with fluid loading for prerenal renal failure and as therapy for rhabdomyolysis. She was then transferred to the intensive care unit (ICU) for observation, and given vitamin B12 replacement therapy and methionine. Her acute prerenal failure resolved with rehydration, and she was given an intravenous heparin infusion as anticoagulation therapy for bilateral proximal DVT, and subsequently given warfarin for a target international normalised ratio of 2.0–3.0. Further imaging, such as a ventilation–perfusion scan for the presence of PE, was not performed as it would not have contributed to her management. After 2 days in the ICU, she was transferred to a general medical unit. An MRI scan on review 2 weeks after her admission showed an increased T2 signal within the posterior columns of the spinal cord. She slowly regained partial motor function of her limbs and normal sensory levels over the following 5 months. She was discharged after 7 months of rehabilitation and inpatient care. She was able to walk short distances, with the aid of a walking frame, but had residual neurological deficits affecting the distal lower-limb muscle groups. DiscussionNitrous oxide is a colourless, odourless gas with a weak anaesthetic but useful analgesic action.1 It is used during short, painful procedures. Because of its ability to elevate mood, nitrous oxide is colloquially known as “laughing gas”, and is a common drug of misuse. “Nagging” or “nanging” are terms used to describe the recreational use of nitrous oxide, derived from the repetitive sound distortions experienced by nitrous oxide users.2,3 In a New Zealand survey of first-year university students, 57% were aware of its recreational use and 12% used it regularly.2 Nitrous oxide is readily available from most supermarkets and online, as it is used as the aerator and propellant for whipped-cream dispensers. The average bulb used for aerating whipped cream contains 8 g of nitrous oxide. Pathophysiology and diagnosisSubacute combined degeneration of the spinal cord is a recognised complication of vitamin B12 deficiency or of nitrous oxide exposure (with or without pre-existing normal vitamin B12 levels). This complication is well documented in anaesthesia literature in relation to frequent nitrous oxide exposure in anaesthesia, such as during multiple operations, or analgesic use for repeated dressing changes for burns patients.4,5 Patients with long-term nitrous oxide recreational use are reported to have neurological symptoms ranging from paraesthesias to incoordination and autonomic dysfunction.6-9 There is no known neurological toxicity threshold for nitrous oxide exposure. Toxicity is related not to the frequency or level of nitrous oxide exposure, but to the patient’s levels of vitamin B12. Spinal cord degeneration resulting from a single short exposure to nitrous oxide anaesthesia, in association with vitamin B12 deficiency, has been reported.10,11 The neuropathological changes observed in the affected spinal cord include initial swelling and irregularity of the myelin sheath surrounding the nerve cell axons (reversible), followed by frank demyelination and loss of axons (irreversible).12 This occurs in the central regions of the posterior columns and, to a lesser extent, in the posterolateral regions of the spinal cord. The changes manifest as high-signal lesions on MRI T2-weighted scans caused by increased water content secondary to oedema.10,11 Nitrous oxide inhibits the active form of vitamin B12, rendering it unavailable to form the myelin sheath proteins, resulting in axonal swelling and eventual axonal loss. The mechanism of action is the inactivation of vitamin B12 (cobalamin) from its monovalent, active cobalt form (Co+) to the inactive, bivalent cobalt form (Co2+). The irreversibly inactivated vitamin B12 (Co2+) results in failure of methylation of proteins in the myelin sheaths4 and a loss of nerve cell axon integrity.12 Another contributing factor to the toxicity of nitrous oxide is the role of vitamin B12 as a cofactor of the methionine synthase reaction. The enzyme catalyses the reaction in which homocysteine is converted to methionine; tetrahydrofolate is also formed, which is a cofactor in the metabolism of nucleic acids (eg, DNA).9 Thus, nitrous oxide has a direct effect on DNA synthesis, as well as nerve axon integrity. Other postulated mechanisms of action for central nervous system toxicity of nitrous oxide include inhibitory effects on N-methyl-d-aspartate receptors, stimulatory effects on dopamine neurones, stimulation of descending noradrenergic neuronal pathways, provoked release of noradrenaline in dorsal horn neurones, and sympathetic action via α-1-adrenergic stimulation.8,9 A diagnosis of subacute combined degeneration of the spinal cord can be confirmed by MRI, in association with low serum vitamin B12 levels, but in some cases MRI scans show no abnormality.11 The differential diagnoses include demyelination, neoplasms, infections (eg, with Listeria spp., or HIV), myelopathy, and syringomyelia. Treatment and prognosisTreatment involves ceasing nitrous oxide use and giving vitamin B12 replacement therapy. Administration of methionine may also be required as an adjunct, given the direct effects of nitrous oxide on methionine synthase. Exogenous methionine would provide a direct substrate for methionine synthase, while the body slowly replaces the inactive vitamin B12 and commences repletion of endogenous methionine. Two patients receiving vitamin B12 replacement therapy experienced a worsening of their neurological symptoms until the addition of oral methionine, which halted the neurological decline and accelerated their recovery.9 Reported recovery periods vary from 1 week to 1 year. Partial versus full recovery will depend on the extent of the neuropathological damage to the spinal cord; spinal cord oedema and myelin sheath loss will resolve, but axon loss is permanent.

Michaela Cartner MB BS, FACEM · Michael Sinnott MB BS, FACEM, FRACP · Peter Silburn MB BS, PhD, FRACP

A 52-year-old woman presented with bilateral soft, reducible anterior neck swellings on coughing, following a recent respiratory tract infection. Plain x-rays of the neck and upper chest showed a normal appearance. Computed tomography of the neck and chest while the patient performed the Valsalva manoeuvre showed bilateral large apical lung hernias, which extended through the thoracic inlet into the root of the neck (Figure). This lung herniation was probably caused by a congenital deficiency in the suprapleural membrane (Sibson’s fascia), combined with increased thoracic pressure created by the respiratory tract infection. Surgical repair was not necessary as the hernias were asymptomatic and not associated with chronic cough.

Jyotsna M Joshi MD

Re: “Influenza outbreak related to air travel”, by Andrew G Marsden, in the 4 August 2003 issue of the Journal (Med J Aust 2003; 179: 172-173). The title should have been “Outbreak of influenza-like illness related to air travel”, consistent with the text.

Andrew G Marsden

Aileen Plant died unexpectedly at Jakarta airport on 27 March 2007, cutting short a life of exceptional achievement. Her warmth and wisdom had touched many people — as a favourite aunt, friend, confidante, researcher, colleague, mentor, and valued health adviser. Yet her influence stretched far beyond Australia. As an adviser and leader in international public health, she was highly regarded by Margaret Chan, now Director-General of the World Health Organization. In the words of David Heymann, a long-time friend, “the world is a better place because of her life”. Aileen Joy Parnell was born in Warrigal, Victoria, on 9 July 1948, the fourth of eight children. She left school at 14 years of age, working on the family farm and then in a bank, before studying medicine at the University of Western Australia. Although her marriage to Roger Plant, a fellow student, ended soon after graduation, she always remained close to the Plant family. In 1977, Aileen worked at Charles Gairdner Hospital in Perth, and then at the Royal Darwin Hospital, where her clinical experiences triggered a life-long commitment to Aboriginal health. After obtaining a Diploma of Tropical Medicine and Hygiene in London, she returned to Darwin in 1982, working for several years as a senior registrar and administrator. Following a period in Sydney as a graduate student, teacher and public health practitioner, she returned to Darwin in 1989 as Chief Health Officer for the Northern Territory. Aileen clearly saw the importance of linking public health practice to research and education. Accordingly, she moved to the Australian National University, Canberra, in 1992 to teach the Master of Applied Epidemiology, which set new standards in communicable disease training in cooperation with government agencies. Aileen returned to the University of Western Australia in 1995 and became Professor of International Health at Curtin University, Perth, in 2000. She was highly influential in communicable disease planning through the Communicable Diseases Network Australia and as Deputy Director of the Australian Biosecurity Cooperative Research Centre. She was also a valued communicable disease adviser for the WHO through the Global Outbreak and Alert Response Network, and became a global troubleshooter, unscrambling disease outbreaks in many countries. With the emergence of severe acute respiratory syndrome (SARS), she was one of the first WHO experts to go to Hanoi, using her expertise to help control the local outbreak. Subsequently, the Vietnamese Government awarded Aileen its highest civilian medal. She also consulted regularly in Geneva, in Canberra and in the region, providing advice to the WHO, Indonesia and other countries on tuberculosis control and influenza surveillance. Aileen collaborated with many other researchers to publish over 90 high-quality articles on tuberculosis, Aboriginal health, migrant health, health services, medical education, and disease surveillance and control. Her outstanding networking skills, learnt as a middle child in a large family, made her an inspirational leader and mentor for many others in later life. Well remembered as a friend and wonderful human being, Aileen was greatly admired for her idealism, integrity, empathy, humility, energy, originality, breadth and depth of intellect, and commitment to evidence. Her capacity to care for people, to work round problems, and also around problem people, underpinned her many achievements. We will particularly miss her sense of humour. She would have appreciated the irony that the ceremony to commemorate her life, attended by family and many friends and colleagues, took place on Friday the 13th of April. Chronic asthma, dating from adolescence, plagued Aileen for much of her life. Her sudden death was attributed to acute haemorrhagic pancreatitis complicating a short gastrointestinal illness. She is survived by her siblings, parents-in-law and 33 nephews and nieces.

John D Mathews

To the Editor: We report two cases of previously well male bodybuilders who presented with severe extrapyramidal reactions after intramuscular injection of the antipsychotic fluphenazine decanoate, in the mistaken belief that it was an anabolic steroid. The first patient, aged 31 years, obtained fluphenazine decanoate from a gym contact. He injected 50 mg intramuscularly on alternate days (Days 1, 3 and 5) to a total of 150 mg, then presented to two local hospitals on Days 7 and 11 with difficulty swallowing, generalised muscle stiffness and lethargy. He withheld the history of fluphenazine use, and was diagnosed with tonsillitis. On Day 14, he presented to our emergency department (ED) with marked dystonia, immobility, and inability to speak or swallow food. On examination, he was afebrile and haemodynamically stable. He was given a trial dose of benztropine 2 mg, but improvement was slight and, given the absence of relevant history, benztropine was not repeated. The neurology team raised the possibility of a conversion disorder, but the psychiatry team, noting the patient’s attempts to speak and an absence of recent stressors, believed that further investigation into an organic cause was required. When the patient’s wife learned that he had used fluphenazine and alerted the neurology team to this use, he was started on regular benztropine and his condition improved over the next 3 days. The dose of benztropine was reduced on discharge, but his dystonia recurred and required readmission to hospital for further treatment. The second, unrelated patient, also aged 31 years, openly admitted purchasing fluphenazine decanoate from “a friend of a friend”. After injecting two 50 mg depots, he had multiple presentations to three EDs, where he was treated for dystonia with immediate doses and then regular low doses of benztropine. On admission to our hospital 19 days after injection, he was afebrile and haemodynamically stable, with marked dystonia. His initial creatine kinase level was elevated (553 U/L; normal, < 204 U/L), but subsequently normalised and was not accompanied by autonomic dysfunction. His condition improved with regular oral diazepam and benztropine, but symptoms recurred when he inappropriately reduced his benztropine dose after discharge. On subsequent review, both patients’ dystonia was resolving, but they had significant akathisia. Inadvertent and inappropriate use of a long-acting phenothiazine not only required prolonged anticholinergic therapy for these men, but we believe placed them at risk of neuroleptic malignant syndrome. We have found no previous similar reports in the medical literature, but are aware anecdotally of at least one other case of a patient treated recently at a district hospital. The anabolic steroid nandrolone decanoate is referred to colloquially on numerous websites and by our patients as “deca” (from the Organon brand name Deca-Durabolin). We believe our patients and their supplier(s) have mistaken the “decanoate” in fluphenazine decanoate for the pharmacologically active component of the drug.

Elizabeth A S Giugni · Rachel S Boddy · Natalie G Limet

To the Editor: The introduction of indoor smoking restrictions in Western Australian pubs, clubs and nightclubs1 has been championed as a public health success and an advance in tobacco control. But how well is it being observed, and is the current legislation adequate? Although smoking in Australia is declining, a report showed that one in seven 16–17-year-olds had smoked cigarettes in the previous month.2 Peer pressure has an important influence on smoking uptake,3 and alfresco hospitality settings, being exempt from the smoke-free restrictions, constitute important risk environments for young people. Moreover, 85% of adults in WA do not smoke, but continue to be affected by second-hand smoke drifting from alfresco balconies, beer gardens and street cafes. Indeed, the legislation risks turning these popular and highly visible entertainment areas into nicotine classrooms4 for the young, and “no-go” zones for health-conscious non-smokers. We set out to evaluate compliance with the smoke-free legislation, and its impact on smoking in licensed premises. Twenty medical students were recruited to monitor smoking in 93 Perth hotels and nightclubs on two Friday evenings during November 2006. Entertainment areas were classified as indoor (smoke-free), semi-outdoor (smoke-free, failing to meet exemption criteria) and alfresco (smoking allowed), in accordance with the new legislation. Average observation times were 20 minutes, 17 minutes and 15 minutes respectively. Indoor compliance with the legislation was high, with smoking noted in only five (5%) of the 93 premises. Whether by default or design, 58 premises (62%) had alfresco areas and there was smoking activity in those areas in 56 (97%) of these premises. Forty premises (43%) also had semi-outdoor areas where, contrary to the legislation, smoking remained prevalent (23 premises; 57.5%). Overall, smoking was observed in 69 of the 93 premises (74%). In 35 of these premises (51%), smoking was visible to the passing public. These results demonstrate the inadequacy of the new smoke-free legislation in restricting smoking, protecting the health of non-smokers and strengthening tobacco control. The legislation has been well accepted, but smoking (legal and illegal) remains prevalent in licensed premises. This presents a serious challenge to tobacco control and efforts to reduce smoking by young people. A key lesson from the history of tobacco control is that partial bans achieve partial results.5 A complete ban on smoking, both inside and outside licensed premises and restaurants, is urgently required.

William J Patterson · Michael M Daube · Stephen L G Hall · Denitza Moronova

To the Editor: Bajorek et al1 did not address two aspects of compliance that may be an issue in community care of patients with atrial fibrillation taking warfarin: time of dose, and point-of-care testing. There is no pharmacological reason requiring warfarin administration in the evening. This practice arose to facilitate dose adjustment on the day of testing, initially in hospitals, and subsequently flowed on to community care. We know that compliance is better with once-daily administration re-gimens, and this patient group invariably needs other medications, such as diuretics, that require morning doses. Concomitant morning administration of warfarin would be logical. In addition, it would reduce attendances by domiciliary nurses to cognitively impaired patients, who may otherwise require twice-daily visits for administration of medications. This would alleviate a significant burden on this stretched resource. The implementation of point-of-care testing at the general practitioner’s surgery by a registered nurse can be of great benefit in the liaison required to manage therapy, and facilitates instant dose adjustments by the doctor, who has comprehensive knowledge of the patient’s pharmaceutical and health circumstances.2

Peter W Ford · Angela Close

In reply: I thank Ford and Close for highlighting additional points regarding the optimal management of anticoagulants in general practice. Indeed, neither of these points was raised by our study participants. Regarding the timing of doses, for medication safety reasons, in many hospitals the warfarin dose is listed for mid-evening administration; the recently introduced National Inpatient Medication Chart (NIMC), which incorporates a designated “warfarin section”, nominates 16:00 as the time. In the hospital setting, this timing is necessary to enable the treating medical team (rather than after-hours staff) to review the day’s blood test results, and subsequently prescribe the appropriate dose. The process ensures that treatment is optimally managed by those most knowledgeable about the patient’s regimen, prevents dose omissions, and reduces the time to dose stabilisation (and potentially, time to discharge). Ford and Close appropriately point out that this timing may not always be convenient for patients once they are discharged to the community setting. The optimal regimen should facilitate the patient’s adherence to treatment, and therefore should coordinate with the rational use of existing support services. This needs to be more carefully considered in discharge planning when warfarin therapy is involved. Point-of-care testing is an efficient mode of monitoring anticoagulation therapy, but we were unable to expand on this in our previous discussion (due to word limits). Internationally, point-of-care testing underpins many comprehensive monitoring services, whereby allied health professionals (eg, trained nurses or pharmacists) perform the blood tests, monitor results, adjust doses, and/or prescribe therapy, as well as educate patients, under the guidance of a medical officer. Such services are conventionally offered on an outpatient basis (eg, the Antithrombosis Center, University of Illinois Medical Center, Chicago, Ill, USA) or within the general practice setting, and are effective and safe models of care. Patient self-management using point-of-care testing devices has also been studied overseas,3 with reports of good control of international normalised ratio (INR) and high patient satisfaction. Locally, point-of-care testing has been trialled within community pharmacies. In a Sydney-based study, trained community pharmacists monitored INRs using point-of-care testing, reviewed doses according to standardised nomograms, and subsequently liaised with GPs regarding dose adjustments. The results showed that collaborative management effectively maintained INRs within the therapeutic range.4 There is scope to develop such models further, and we are currently investigating GPs’ preferences for models of care, as well as opportunities for mobile anticoagulation services.

Beata V Bajorek

To the Editor: In a recent article,1 Scrimgeour showed the differences between death rates in Aboriginal people and in the general Australian population. He used the Accessibility/Remoteness Index of Australia (ARIA)2 to show that Aboriginal people in remote areas generally had higher death rates than those near major health facilities. However, this widely used tool is inaccurate when applied to some health facilities. Cherbourg Aboriginal community (population about 2600) is located in the South Burnett district of south-eastern Queensland, 260 km by road from Brisbane. It has a 10-bed hospital with two resident doctors. There are several small towns (population 1000–3000) in the district. Two have hospitals with no full-time medical staff. The main centre is Kingaroy (population about 12 000), 50 km from Cherbourg. It has a 60-bed hospital with resident staff, but no specialists or consultants. There are general practitioners but no medical specialists in the district, although some specialists visit for a day or so per month. Most patients needing specialised services go to public hospitals in Brisbane (220 km away [from Kingaroy]), Toowoomba (170 km away) or Nambour (140 km away), where waiting lists are long. Children go to children’s hospitals in Brisbane, either by road (a 3-hour journey) or by helicopter. The ARIA index ranges from 0.0 (major city) to 12.0 (very remote area). Cherbourg (classed with Murgon, 5 km from Cherbourg) has an index of 2.9 and Kingaroy, 2.6. The cities of Darwin, Cairns and Townsville, all with major hospital and health facilities, have an ARIA index of 3.0, while Alice Springs, which also has a major hospital and specialists, has an ARIA index of 6.0. Clearly, the remoteness index is not a good indicator of the availability of local specialist health services. The ARIA classification is widely used. The anomaly of the South Burnett and Cherbourg Community may (or may not) be the only problem with the index. Until such anomalies are corrected and ARIA is validated, any results derived using the index should be treated with caution.

Alan E Dugdale

To the Editor: The Guidelines for the management of acute coronary syndromes 20061 state: “Enoxaparin may be used in conjunction with fibrin-specific fibrinolytic agents in patients under the age of 75 years, provided they do not have significant renal dysfunction. An intravenous bolus dose of 30 mg followed by a 1 mg/kg subcutaneous injection every 12 hours in combination with tenecteplase is the most comprehensively studied therapy.”1 In Australia, enoxaparin is not licensed for intravenous use (Tony Hall, Team Leader, High Risk Medications and Systems, and Christine Maclean, Associate Director, Safe Medication Practice Unit, Queensland Health, personal communication) and there is no recommendation for the intravenous use of enoxaparin in the drug product information.2 Are the authors recommending “off-label” use of intravenous enoxaparin, or do they wish to modify the guidelines to reflect what the management should be if clinicians are unable to use intravenous enoxaparin?

Mark Little · Chris Johnstone

In reply: The guidelines were published to provide clinicians with the most contemporary information on the management of acute coronary syndromes based on the international literature, and may include treatments which are not currently available, officially licensed or available through the Pharmaceutical Benefits Scheme in Australia. In the context of adjuvant therapy for patients with ST-segment-elevation myocardial infarction (STEMI), the guidelines recommend that antithrombin therapy should be used with fibrin-specific fibrinolytic agents.1 Based on the best evidence available at the time, the guidelines mention two antithrombins, unfractionated heparin and enoxaparin, to be considered for use in this setting. The recommendation for enoxaparin is based on comprehensive evidence of clinical benefit with the regimen of an initial intravenous (IV) bolus dose followed by subcutaneous injections every 12 hours. It is up to individual practitioners to determine whether the IV dose should be provided “off-label” or omitted, based on the evidence and the circumstances of the individual patient and setting. The issue of superiority of enoxaparin over unfractionated heparin as adjuvant therapy for patients with STEMI is currently being evaluated in light of recent evidence,2 and will be included in a future update of the guidelines.

Constantine N Aroney · Philip Aylward

To the Editor: I read with great interest the recent updated review of amoebiasis by van Hal and colleagues1 and their previous letter2 describing three cases of locally acquired amoebiasis due to Entamoeba histolytica in Australian men who have sex with men (MSM). These articles should alert clinicians to the emergence of invasive amoebiasis and the possibility of person-to-person transmission of E. histolytica through oral–anal or oral–genital sex among MSM in developed countries. The same phenomenon has been reported in Taiwan3 and Japan.4 The prevalence or incidence of intestinal amoebiasis among people at risk may have been underestimated in the past, as microscopy of stool specimens has lower sensitivity and specificity than E. histolytica antigen detection methods for diagnosing the disease.1,5 Cases of amoebiasis may evade detection using the diagnostic algorithm proposed by van Hal and colleagues,1 which suggests using microscopy of stool specimens to detect E. histolytica complex followed by confirmation with specific antigen detection methods or molecular methods. To increase diagnostic sensitivity and specificity, I suggest revising the diagnostic algorithm for intestinal amoebiasis in developed countries to include more accurate first-line detection methods. For example, specific antigen detection methods or polymerase chain reactions, as proposed by Tanyuksel and Petri,5 could be incorporated.

Chien-Ching Hung

To the Editor: van Hal and colleagues deserve congratulations for their lucid, concise and timely review of the complex problem of human amoebic infection and its diagnosis.1 Not surprisingly, however, their article raises more questions than it answers. To me, the gist of their message was as follows: what was in the past diagnosed as Entamoeba histolytica infection, based on the microscopic identification of organisms from faeces, culture or histological sections, actually may have been caused by other species, viz. E. dispar (a recently described non-pathogen) or E. moshkovskii (known for a long time from sewage samples, but only recently found to infect humans). Because these species are all identical morphologically, they can be distinguished reliably only by sophisticated molecular techniques. To complicate matters further, despite E. dispar having been virtually defined as the “non-invasive form” of Entamoeba, most true E. histolytica infections are still asymptomatic.2 Not only the parasite, but also individual host factors (perhaps including genetics), determine pathogenicity. Thus, not all people infected with the same pathogenic strain will manifest symptoms or signs of invasive disease. Given their biology and evolution, it is conceivable that, eventually, invasive strains of even E. dispar will be discovered! Furthermore — and this seems not to have been investigated yet — mixed infections involving different species and strains of these parasites almost certainly occur (not to mention the “traditional” non-pathogenic amoebae, which frequently do occur in mixed infections). The authors advocate treatment of even asymptomatic E. histolytica infections, but how would these be detected outside epidemiological surveys or healthy population screening programs? Given the difficulty and expense of specifically identifying the infective organism even in symptomatic cases, and the relative cheapness of treatment, surely it would be sufficient simply to treat on the basis of clinical presentation plus the identification of E. histolytica-like parasites, with or without objective evidence of histopathology. Anything more could be justified only within the context of a well funded and carefully designed research program and/or epidemiological study.

Paul Prociv

In reply: We agree with Hung that molecular and antigen testing methods are more sensitive for Entamoeba histolytica detection than microscopy and that reliance on microscopy alone would result in under-detection. Our algorithm1 was presented the way it was for several reasons. Firstly, both molecular and antigen testing are significantly more expensive than microscopy. Secondly, as these tests can currently only detect a single pathogen, they would not replace microscopy. Most patients, especially men who have sex with men (MSM), have multiple intestinal parasites, so the more specific methods would remain an adjunct in parasite detection.2 Thirdly, the positive predictive value of any test is dependent on the prevalence of the disease. The prevalence of E. histolytica in Australia, based on current data, is less than 1% in high-risk populations, including MSM. Thus, at present, molecular and antigen tests would be more likely to give false positive than true positive results. However, we agree that our algorithm could be modified as suggested if prevalence rates were between 5% and 10%. Finally, as seen in the MSM population in Taiwan, this is not a static situation, and ongoing local surveillance is required.3 We agree with Prociv that, before the introduction of molecular techniques, E. histolytica prevalence would have been overestimated. We also agree that specific host factors and/or undefined parasitic virulence factors can lead to invasive disease. However, given the extensive molecular work that has been undertaken, we believe it unlikely that invasive strains of E. dispar will be discovered.4 Furthermore, recent studies show that mixed infections are common.2,5 In symptomatic patients, empirical amoebicidal therapy is warranted. However, to ensure that alternative diagnoses (eg, inflammatory bowel disease) that require different treatment are not overlooked, all attempts to accurately speciate Entamoeba complex should be undertaken. We acknowledge that speciation using the polymerase chain reaction is beyond the means of most laboratories, but this is not the case for enzyme immunoassay testing of stool samples, which is rapid, sensitive and relatively cheap. For asymptomatic patients who are carriers of E. histolytica cysts, the World Health Organization recommends treatment.5 However, in areas of low prevalence such as Australia, Entamoeba cysts are more likely to be non-pathogenic E. dispar or E. moshkovskii species than E. histolytica.3 Thus, in Australia, treatment would be unnecessary in a high proportion of patients. Furthermore, therapy requires a luminal agent (paramomycin), which is difficult to obtain. The most practical solution is to either give no treatment or to treat only those patients who have tested positive for E. histolytica.

Sebastiaan J van Hal · Damien J Stark · Debbie Marriott · Jock L Harkness

To the Editor: Two recent articles in the Journal touch on the current plight of medical academics. Hays emphasises the need to reassert the role of teaching in academic medicine — otherwise, “our aim to produce safer, more efficient doctors will be under threat”.1 Joyce and colleagues outline the projected increase in the number of graduates from Australian medical schools, although their concern is more for the post-graduate careers of these young doctors than for their initial clinical training.2 In 2006, Van Der Weyden warned that not only do new ways of teaching medical students need to be rapidly explored but also that more skilled teachers must be found and trained.3 Medical students themselves believe that more clinical teachers are required to ensure that the increasing numbers of students are taught effectively.4 From personal experience we know that, while many full-time clinicians are both willing and inspiring teachers at undergraduate level, a core of permanent academics is needed to direct teaching during these clinical years. But why would anyone choose to be a medical academic today? Certainly not for the money — a recently qualified obstetrician/gynaecologist, starting at senior lecturer level after about 15 years of training, is looking at an income of less than half that of a staff specialist at the same level, and a quarter of that possible in private practice. One day of private practice per week does not help — obstetrics is a full-time commitment, and even in gynaecology the need to pay practice and indemnity costs outweighs any financial benefits. Is it the kudos? Adjunct academic titles are easily gained by non-academics: hospitals are awash with adjunct associate professors and lecturers. The adjunct appointment system often lacks regular and critical appraisal, and in some cases titles are used to the professional or financial gain of the recipient, with little reciprocal input into teaching at the institution concerned. (However, there are indications of attempts to crack down on such practices.)5 The lifestyle then? Academics may have a less frenetic clinical schedule, but the continuing pressure to produce quality research and to jump increasingly higher hurdles to obtain grants can mean that the limits of the working week are much less defined than for our staff specialist colleagues. We have seen many colleagues depart academia in the past few years for the more verdant pastures of full-time clinical practice. While we are in agreement with Hays about the need for more research into how best to design medical education, we believe that, unless there are urgent improvements in the remuneration, career structure and professional regard for clinical academics, the core workforce of skilled teachers so clearly needed for incoming students will just not be there to deliver that education.

Ajay Rane · Caroline de Costa

To the Editor: Like Haley’s father,1 I too lament the fact that Latin terms have fallen out of use in medical terminology. I also think it retrograde that Latin is being taught to fewer and fewer of our secondary students, as they are missing out on an opportunity to learn so much more about our own language, let alone terms that they might use later in their clinical practice. However, I do not think that it was Latin that helped the young teacher out of a difficult predicament in the 1950s. I can assure Haley that “pseudocyesis” is all Greek to me.

Peter Piazza

To the Editor: Thank you for the charming letter about “non-pseudocyesis” published in the 19 March issue.1 It reminded me of the Brander Matthews quote: “A gentleman need not know Latin, but at least he should have forgotten it.” This is particularly apt, as the term “pseudocyesis” is from Greek.

James Mitchell

To the Editor: The tale told by Katherine Haley’s father about his clever advice on how to protect the privacy of a young pregnant woman makes a good story.1 However, while “non” is a Latin word, “pseudocyesis” is very good Ancient Greek (ψευδοκύησις). Queen Mary I (“Bloody Mary”), who was believed for many months to be with child but ultimately returned to court childless, may have suffered from pseudocyesis. I agree with Dr Haley’s opinion about the lamentable decline in the use of both Latin and Greek terms in medical practice. I take the time to teach my students, residents and registrars enough Latin and Greek to render classical plurals correctly (eg, fistulae, diverticula, carcinomata). Whether they take any notice of this classical teaching is another matter.

William E M Renton-Power

To the Editor: I was both delighted and a little perturbed to read the recent letter by Katherine Haley about her general practitioner father who outsmarted the Department of Education by a medical sleight of hand, stating that his patient had “non-pseudocyesis”.1 However, it was not Latin, but Greek, that did the trick. Despite Dr Haley’s background in Latin, he, like all physicians, had unwittingly used Greek during his medical course. I was fortunate to do a year of Ancient Greek during my undergraduate medical course and, like my late GP father, also did Latin for matriculation. It is unfortunate that Greek is no longer taught in Queensland schools, and Latin only in a few. I believe that we are the poorer for this, and it shows in all sorts of ways, including a general decline in literacy even at the tertiary level. A classical grounding demands scholarship and precision. I have found that knowledge of both Greek and Latin has enriched my knowledge of English literature and Western philosophy, as well as French. Such a grounding also trains the mind in analytical and ordered thought and provides greater insight into the workings of syntax and grammar and a greater facility with words — the building blocks of our language, many of which are derived from Greek and Latin. At the risk of stating the obvious, I will remind readers that anatomical words in medicine are predominately Latin or Greek and that the names of nearly all symptoms and diseases are Greek (with some exceptions, such as “angina pectoris”). In Dr Haley’s time, it was common for potential doctors to receive an arguably more “polished” education that embraced one or two languages, including Latin and, in some private schools, Greek. Alas, the current system of medical student selection favours those “idiots savants” who excel in mathematics and science and not the arts. With respect, I would like to point out that in the term “non-pseudocyesis”, the only Latin component is “non”, the rest being Greek (ψευδής, false; κύησις, pregnancy). For both the enthusiast and the non-classicist, may I recommend my father’s 5th edition of Gould’s medical dictionary (1943), which contains the etymology of every medical word.

Roger K A Allen

Drugs direct Direct-to-consumer advertising of prescrip-tion drugs has come under pressure in the United States, with researchers suggesting that the Food and Drug Administration (FDA) has fallen behind in enforcement of laws regulating such advertising. A study of trends in pharmaceutical spending reveals a staggering US$29.9 billion spent on drug advertising in 2005, with spending on direct-to-consumer advertising increasing by 330% to over US$4 billion since 1996. In the midst of calls for tighter controls on direct adver-tising, the study shows that manufacturers of proton-pump inhibitors, statins, and erythropoietin medications spent about a third of their total marketing budget on direct advertising in 2005. New drugs developed to treat chronic conditions are the most likely candidates for this type of promotion, with most being advertised directly within a year of their introduction into the market. The authors comment that this may lead to increased use of drugs with uncertain safety profiles. A decline in the number of regulatory actions by the FDA against com-panies marketing direct to consumers has led researchers to speculate that the FDA has fallen behind in the task of reviewing and policing inappropriate and misleading advertising. They suggest that this may be the result of insufficient FDA staffing levels and the introduction of more complicated requirements before warning letters can be issued to pharmaceutical companies. N Engl J Med 2007; 357: 673-681 Good bacteria for diarrhoea The efficacy of probiotics in the treatment of diarrhoea in children is related to the strain of bacteria in the preparation, according to Italian researchers. Their randomised clinical trial involved over 500 children aged from 3 to 36 months presenting with acute diarrhoea of less than 48 hours’ duration to a family paediatrician. In the Italian health system, family paediatricians care for children up to 12 years of age. A control group received oral rehydration alone, and five treatment groups were given various oral formulations of probiotic bacterial strains for 5 days. Primary outcome measures were total duration of diarrhoea and the number of stools per day and their consistency. When compared to the control group, the duration and severity of diarrhoea was significantly lower in children receiving Lactobacillus rhamnosus GG and in those receiving a bacterial mix (L. delbueckii var bulgaricus, L. acidophilus, Streptococcus thermophilus and Bifidobacterium bifidum). The authors comment that although there is a possibility of confounders such as parental expectations affecting the findings, the size and resultant power of the study supports the validity of the result. They call for the reclassification of probiotics as drugs rather than food additives, and comment that there is a growing evidence base for the efficacy of these preparations in the treatment of childhood diarrhoea. BMJ 2007; 335: 340 Open season on ’flu The well documented seasonal patterns of human influenza infection in temperate regions may not be as simple or clear-cut in tropical climates, with important ramifications for transmission and the development of pandemic strains. Despite the large amount of data available on the incidence of influenza in humans in temperate areas, little is known about the temporal patterns of human influenza A in east and south-east Asia. In a review by scientists from Australia and France, outbreaks of highly pathogenic avian influenza A (H5N1) were identified and analysed for evidence of seasonality, human infection, and host range. Although outbreaks of disease in humans largely coincided with those in domestic poultry in winter months, several outbreaks in China extended into or re-occurred in the summer. Other Asian countries showed varying patterns of seasonality, and patterns were not uniform across the region. H5N1 isolation from domestic ducks across Asia is steadily increasing. Pandemic strains of the influenza virus can arise by adaptive mutation of zoonotic influenza in a human host, or by genetic reassortment in a person simultaneously infected with a human and an avian strain. When more host species are available, the potential for mutation is increased, as is the risk of pandemic infection in human beings, particularly with close contact between the species. When the season for infectivity in a region is extended, the risk of pandemic is also greater. The researchers comment that the relative timing of human and avian influenza incidence is a key factor in assessing the risk of viral reassortment and subsequent development of a pandemic. Lancet Infect Dis 2007; 7: 543-548

Tanya Grassi