bluuebunny/crossref_metadata_2025 huggingface dataset:
The natural history of left ventricular wall thickening in hypertrophic cardiomyopathy
Authors: Semsarian C. , French J. , Trent R. J. , Richmond D. R. , Jeremy R. W.
Published: March 2008

Abstract Background: Hypertrophic cardiomyopathy (HCM) is associated with mutations of genes coding for major sarcomeric proteins, but the mechanism of hypertrophy is unknown. As hypertrophy may not develop until adolescence, an altered response to physiological growth stimuli may regulate the hypertrophy process.

Aims: This study examined the relationship between age and changes in left ventricular (LV) wall thickness in patients with HCM.

Methods: Forty‐three patients who had definite electrocardiographic and echocardiographic evidence of HCM were studied with serial 2D and M‐mode echocardiograms at least two years apart (mean interval 5.5±3.0 years). LV cavity dimensions, septal and posterior wall thicknesses, and LV mass indices were compared with data from an age‐ and gender‐matched control group.

Results: In patients with HCM aged ten to 20 years (n=9), there was an increase in septal wall thickness during the study period from 15.9±6.2 mm to 19.3 ± 2.1 mm (p<0.01). This increase (3.4±2.5 mm) greatly exceeded the change in septal thickness observed in the control group between the ages often and 20 years (0.8±0.3 mm, p<0.01). There was a lesser increase in posterior wall thickness from 9.8±2.1 mm to 11.5±3.5 mm (p=0.07). In patients with HCM aged 21–40 years (n=11), there was also an increase in septal wall thickness during the study period from 16.0±2.2 mm to 17.8±3.0 mm (p<0.05), but no change in septal thickness in the control group. In contrast, the patients aged >40 years (w=23) showed no significant change in either septal or posterior wall thickness during the study period. LV mass index increased in the ten to 20 years age group from 128 ±24 g/m2 to 164±20 g/m2 (p=0.01), but this increase was not observed in the older age groups.

Conclusions: LV hypertrophy is progressive, particularly in the septum, during adolescence and early adult life in patients with HCM. As progressive hypertrophy may continue after somatic growth has ceased, an abnormal myocardial response to physiological growth regulators is less likely to be the principal stimulus to hypertrophy. Gene‐gene interactions, changes in haemodynamic load or environmental factors may modulate the development of hypertrophy. Serial measurements of ventricular wall thickness in the first two decades of life, and probably until the fourth decade of life are advisable in patients suspected of having HCM.
Reproducibility of brachial ultrasonography and flow‐mediated dilatation (FMD) for assessing endothelial function
Authors: Hardie K. L. , Kinlay S. , Hardy D. B. , Wlodarczyk J. , Silberberg J. S. , Fletcher P J.
Published: March 2008

Abstract Background: High‐resolution brachial artery ultrasonography is used to study vasodilator response induced by physiologic reactive hyperaemia. We examined the reproducibility of measuring flow‐mediated dilatation (FMD) on two occasions.

Aims: To determine the degree of variability of this technique in our vascular laboratory for the design of clinical research studies.

Methods: Nineteen subjects were studied on two separate occasions using an Acuson 128 ultrasound device and a 7.0 MHz linear array transducer. Reactive hyperaemia was induced in the brachial artery by inflation and release of a blood pressure cuff. Nitrate‐induced dilatation was assessed in 11 of the 19 subjects. Measurements were made by two observers blinded to subject details.

Results: The 11 subjects given sublingual GTN during the first ultrasound study had a mean nitrate‐induced dilatation of 20.7% (sd 9.6). The mean vessel diameter of 3.78 mm (sd 0.7) at rest and 3.89 mm (sd 0.7) during reactive hyperaemia yielded a mean FMD of only 3.0% (sd 2.7). The mean difference in FMD within‐observers was 0.13% (sd 2.07), between‐observers 0.06% (sd 2.17) and between‐studies was 0.57% (sd 6.83).

Conclusions: The reproducibility of FMD measured by brachial artery ultrasound was poor and likely to render the measurements inaccurate for clinical research in our hands. Between‐study variation contributed the largest proportion of total study variability. We suggest that investigators using this technique conduct their own careful reproducibility studies in order to avoid the misinterpretation of ‘negative’ studies.
Cross‐reactivity to porcine factor VIII of factor VIII inhibitors in patients with haemophilia in Australia and New Zealand
Authors: Lloyd J. V. , Street A. M. , Berry E. , McPherson J. , Ekert H. , Lammi A. , McWhirter W. R. , Duncan E. M. , Maxwell E. L. , Rowell J. , Baker R. I. , Leahy M. F. , Jupe D.
Published: March 2008

Abstract Background: Inhibitory antibodies which neutralise factor VIII develop in 10–20% of individuals with inherited haemophilia A and rarely as autoantibodies in normal individuals to cause acquired haemophilia. The antibodies are directed against human factor VIII but cross‐react to varying degrees with porcine factor VIII. Porcine factor VIII can be used for treatment in individuals with low cross‐reactivity.

Aims: To determine the cross‐reactivity of factor VIII inhibitors between human factor VIII and porcine factor VIII, in a population of patients with inherited and acquired haemophilia A. Also, to determine whether patients with inherited haemophilia and inhibitors have a higher incidence of factor VIII gene inversion in intron 22.

Methods: Samples and data sheets from 43 patients with inherited and ten with acquired haemophilia were submitted from hospitals in Australia and New Zealand. Inhibitor levels to human and porcine factor VIII were measured by the Bethesda method in 39 with inherited and nine with acquired haemophilia A.

Results: Of 39 patients with inherited haemophilia A, cross‐reactivity was 0% in 17 patients,1–19% in six, 20–39% in 11 and 40–80% in five. In six of nine patients with acquired haemophilia cross‐reactivity was 7%. In inherited severe haemophilia A, the frequency of the intron 22 inversion was not greater in 37 study patients than in 28 patients without an inhibitor.

Conclusions: Many patients in Australia and New Zealand with inhibitors to human factor VIII presently show a low or absent level of cross‐reactivity to porcine factor VIII. These may respond to treatment with this concentrate at least in the short term. There remains a group of patients with high cross‐reactivity who will respond only to recombinant factor Vila or prothrombin complex concentrates.
Is a standard regime for anticoagulation with heparin in unstable angina adequate?*
Authors: Duffy M. , Kelly A. M. , Bau S. , Rosengarten P.
Published: March 2008

Abstract Aim: To establish the proportion of patients with unstable angina in whom adequate anticoagulation is achieved using a standard regime of intravenous heparin.

Method: A prospective series of 108 Emergency Department attendees over a six‐month period with a clinical diagnosis of unstable angina for whom anticoagulation with heparin was prescribed were included in the study. The standard regime was a 5000 unit bolus followed by an intravenous infusion of 1000 units per hour (1200 units if the patient's weight was greater than 80 kg), with subsequent adjustments being made by reference to a nomogram. The activated partial thromboplastin time (APTT) was measured at six and 12 hours after treatment began. Two commonly used criteria for adequate heparinisation were compared: 1. APTT greater than 1.5 times control and 2. APTT in the range 60–85 seconds.

Results: There were valid data for 90 patients at six hours and 79 at 12 hours. Compared to the criterion for adequate anticoagulation of APTT greater than 1.5 times the control, 25% of patients were subtherapeutic at six hours and 12% at 12 hours. Compared to the criterion APTT greater than 60 seconds, 53% of patients were subtherapeutic at 6 hours and 47% at 12 hours. At 6 hours, 26% of patients were over‐anticoagulated as defined as APTT greater than 85 seconds. This had reduced to 13% by 12 hours.

Conclusions: In the context of recent research suggesting that an APTT of greater than 1.5 times the control is sufficient to reduce complications in unstable angina, our results demonstrate that a standard regime of heparinisation will achieve this goal in the majority of patients within 6 hours of starting heparin therapy. However, if an APTT of 60–85 seconds is the goal, this standard regime is inadequate.
Asthma prevalence, morbidity and management practices in South Australia, 1992–1995
Authors: Adams R. , Ruffi R. , Wakefield M. , Campbell D. , Smith B.
Published: March 2008

Abstract Background: The Spring South Australian Health Omnibus Survey (SSAHOS) has been used to monitor trends in asthma prevalence, asthma morbidity and asthma management practices between 1992 and 1995.

Aims: To determine if self‐reported asthma prevalence and availability of asthma action plans were increasing. To identify deficiencies in asthma management and opportunities for intervention.

Methods: Representative population survey by trained interviewers using a multistage, systematic, clustered area sample of 4200 households in South Australia where people aged 15 years or more are living.

Results: Over 3000 interviews were conducted each year. Between 1992 and 1995 the self‐reported prevalence of asthma in those aged 15 years or more increased significantly from 15.7% to 20.3% (p<0.0005), and the prevalence of current asthma increased from 9.3% to 11.4% (p<0.05). The self‐reported availability of individual asthma action plans increased from 21.9% in 1992 to 42.2% in 1995 p<0.0005). In 1992, 21% had a nebuliser at home, and 10.5% had a peak flow meter. In 1993, 61.4% were using preventive medications, and 35% thought bronchodilators were ‘;preventer’ medications. In 1994 and 1995, between 12.5% and 15.6% had nocturnal awakening weekly or more often, and 31.4% had morning asthma symptoms weekly or more often. Between 20.1% and 20.8% had lost days from usual activities during the last year. Those on incomes below $20,000 had more symptoms, had more admissions to hospital, and required more medication than those on higher incomes.

Conclusions: Self‐reported asthma prevalence has increased. There remains a gap between current asthma management and that recommended by the National Asthma Campaign.
Establishing a programme for continuous ambulatory infusion chemotherapy
Authors: Cox K. , Murray B. , Visintin L. , White G. , Kovac S. , Storey D. , Childs A. , Findlay M. , Kelleher H.
Published: March 2008

Abstract Background: The development of venous access devices (VADs) and portable infusion pumps has enabled chemotherapy to be administered continuously within the home environment.

Aim: The objective of this study was to describe the experience of establishing an ambulatory chemotherapy programme for patients receiving protracted infusions (PVIs) of 5‐fluorouracil (5‐FU).

Methods: The files of all patients receiving PVI 5‐FU as a component of their treatment for gastrointestinal malignancy were reviewed. The types of VADs, infusion pump systems and their management were documented. Information packages and education programmes were developed for patients.

Results: Seventy‐four patients with gastrointestinal cancer were studied. At the end of the review period the Portacath was the preferred VAD, while both pumps used were found to have advantages and disadvantages. The choice of pump was decided more by patient preference than systematic differences in performance of the pumps.

Conclusions: The findings in this review confirm that, with close attention to the potential pitfalls of ambulatory chemotherapy, an acceptable service can be provided.
Ten‐year follow‐up of a cohort with rheumatic heart disease (RHD)
Authors: Carapetis J. R. , Walker A. R. , Kilburn C. J. , Currie B. J. , MacDonald K. T.
Published: March 2008

Abstract Background: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) occur at among the highest rates in the world in Aboriginal Australians of the Northern Territory.

Aims: To follow‐up a previously‐described cohort of Aboriginal children with RHD, in order to understand better the outcome of ARF and RHD in this population, and to identify areas where the impact of these diseases might be lessened

Methods and results: Of a cohort of 33 children seen between 1980 and 1984, 27 survived until July, 1984. Twenty‐five of the survivors were followed up for a mean of 10.6 years to a mean age of 24.1 years. The two deaths during follow‐up were both due to RHD. Six people underwent valve replacement surgery; all were clinically healthy when last seen. Complications included two thromboembolic events and two episodes of endocarditis. Deterioration of RHD severity was associated with ARF recurrences (relative risk 3.6; 95% CI 1.7–7.6), and resolution of RHD was associated with having only mild valve lesions initially (risk difference 0.58; 95% CI 0.30 to 0.86). During follow‐up, valve lesions tended either to resolve or to become more complex and severe, with a higher proportion of aortic valve lesions and multiple valve lesions. Of seven children with suspected past ARF, excluded from the original cohort because of normal cardiac findings at the time, three developed RHD, including one who died due to RHD and two with moderate or severe valve lesions.

Conclusions: In Aboriginal Australians, poor outcomes of RHD are common, and are associated with ARF recurrences and early onset of more severe valve lesions. A coordinated ARF and RHD control programme is needed in this region, using a centralised register of patients, and concentrating on strategies to improve adherence to secondary prophylaxis regimens, better clinical care (including newer surgical techniques) and education of patients, families, and health staff.
Factors influencing the outcome of donor marrow transplantation in adults from less than ideal donors: experience from two Australian centres
Authors: Grigg A. , Morton J. , Durrant S. , Bardy P. , Szer J.
Published: March 2008

Background: This paper reports the results of 78 marrow transplants in two Australian hospitals between 1991 and 1996, using unrelated (n=54) or mismatched related (n=24) donors. Twenty‐six patients received granulocyte‐macrophage colony stimulating factor (GM‐CSF) post‐transplant as part of a phase II study. Fifty‐four patients (74%) had advanced disease.

Aims: To identify factors associated with a superior outcome post‐transplant, to evaluate the effect of GM‐CSF on engraftment and other transplant parameters, and to compare the overall results with those of published series.

Methods: Review of patient records, a Medline search of the relevant literature and appropriate statistical analysis.

Results: The probability of overall survival and event‐free survival (EFS) at three years was 35 ±6% and 22±6% respectively. Pre‐transplant factors significantly associated with an inferior EFS were advanced disease, poorer performance status and age >30 years. The EFS in patients with standard risk disease was 51 ±13%versus 10±5% in patients with advanced disease, p<.0001. Severe acute graft‐versus‐host disease was also associated with a poorer outcome. Neutrophil engraftment was faster in patients who received GM‐CSF but there was no difference in any other transplant parameters.

Conclusions: These results are consistent with reported series elsewhere and suggest that an extended family or unrelated donor transplant should generally be limited to patients with a good performance status and early phase but otherwise incurable haematological disease.
Experience with the use of continuous positive airway pressure (CPAP) therapy in the emergency management of acute severe cardiogenic pulmonary oedema
Authors: Kelly A.‐M. , Georgakas C. , Bau S. , Rosengarten P.
Published: March 2008

Background: Acute pulmonary oedema (APO) is a frequent cause of respiratory failure and a common reason for presentation to emergency departments (EDs). To date, no paper has been published on the application of continuous positive airway pressure (CPAP) therapy for a large broad‐based patient group.

Aim: To report our experience with the use of CPAP in severe APO oedema, with particular reference to safety, intubation rates and impact on EDs' resources.

Method: A retrospective chart review was undertaken of 75 patients with acute severe pulmonary oedema who were treated with adjuvant CPAP in an urban teaching hospital ED.

Results: Three patients (4%) required subsequent endotracheal intubation and mechanical ventilation. The average duration of CPAP was 1.9 hours. Eighty nine per cent of patients experienced no adverse events while being treated with CPAP. Five patients failed to tolerate the tight fitting mask necessitating removal of CPAP, three patients experienced arrhythmias related to underlying cardiac disease and two patients experienced mild transient hypotension. Seventy one per cent of patients were discharged from the ED to general medical wards. The in‐hospital mortality for patients treated with CPAP was 15%.

Conclusion: This series has demonstrated that CPAP therapy delivered via a face mask for the treatment of acute severe APO is safe and effective when applied to a broad range of patients. We recommend the use of CPAP therapy for all suitable patients presenting in severe APO irrespective of age or underlying pulmonary disease.
Multiple cycles of aggressive chemotherapy prior to autologous peripheral stem cell transplantation for lymphoma
Authors: Goss G. , Szer J. , Basser R. , Fox R. , Grigg A.
Published: March 2008

Background: Based on in vitro evidence of synergy between certain chemotherapeutic agents and of improved efficacy of cytotoxics administered as continuous infusions we devised a novel chemotherapy regimen for use in patients with lymphoma.

Aims: To assess the efficacy and tolerability of this regimen alone and in combination with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory lymphoma.

Methods: The regimen consisted of cytosine arabinoside and etoposide given as five day continuous infusions, bolus doses of methotrexate and cyclophosphamide and four days of oral dexamethasone (MADEC), together with prophylactic G‐CSF. Fifty‐one patients aged 17 to 65 years (median 43) were treated; 34 had intermediate or high grade non‐Hodgkin's lymphoma and 17 had Hodgkin's disease. Patients with responsive disease received a second cycle.

Results: Eleven patients (22%) achieved a complete response and 19 patients (38%) achieved a partial response, eight of whom were gallium negative. Previous chemosensitivity was highly predictive for response; minimal response was seen in patients with primary refractory disease. The probability of survival and event‐free survival at 40 months for the entire group is 46% (±8% SEM) and 26±8% respectively. Thirty‐one patients proceeded to ASCT; the probability of survival of the transplanted group is 65 ± 11 % at 40 months. The regimen caused significant myelosuppression. The majority of cycles were complicated by febrile neutropenia and the requirement for platelet and red cell transfusions. Non‐haematological toxicity was predominantly mucositis and was generally mild.

Conclusions: MADEC is a highly active regimen in patients with relapsed lymphoma. Patients responding to MADEC who proceed to ASCT have a good chance of achieving a durable remission.
Radiofrequency catheter ablation in symptomatic ventricular arrhythmia
Authors: Raungratanaamporn O. , Nutakul T. , Chotinaiwattarakul C. , Sriyaphai W. , Chaithiraphany S. , Bhuripanyo K. , Mahanonda N. , Hongvisitgul C. , Kangkagate C.
Published: March 2008

Background: Radiofrequency catheter ablation (RFCA) is an effective method to cure both supraventricular and ventricular arrhythmia (VA) in certain centres.

Aim: To assess the results of RFCA in VA at Siriraj Hospital.

Method: Electrophysiologic study, mapping, using both earliest endocardial activation and pace mapping, and ablation were performed.

Results: Thirty patients with symptomatic VA underwent RFCA. The mean age was 44 years. Eight patients had underlying heart disease (two prolapsed mitral valve, three myocarditis, two dilated cardiomyopathy and one mitral stenosis). Thirty‐six morphologies of VA were detected from the study. Thirty‐three morphologic tachycardias attempted were successfully ablated; 17, 10 and six were right VT, left VT and premature ventricular contraction (PVC), respectively. Failure of ablation occurred in one patient with left VT. Only minor complications occurred in this study.

There was no difference in cycle length and endocardial activation time between right and left VT. 12/12 identical pace mapping was more easily performed in right VT than in left VT The fluoroscopic and procedure times in left VT were significantly longer than in right VT.

Relapse occurred in six patients. Re‐ablation was successfully performed in four patients, giving a final success rate of 93%.
Low‐risk febrile neutropenia in a medical oncology unit
Authors: Leong D. C. S. , Kinlay S. , Ackland S. , Bonaventura A. , Stewart J. F.
Published: March 2008

Background: Febrile neutropenia occurring in patients receiving chemotherapy for solid tumours or lymphoma is usually of short duration, and therefore may have a better outcome compared to patients with acute leukaemia or patients receiving myeloablative chemotherapy.

Aims: To review retrospectively the outcomes for febrile neutropenia occurring in patients of the Medical Oncology Unit at our institution, and to identify factors associated with worse outcome, particularly prolonged admission or death.

Methods: We reviewed 102 episodes of febrile neutropenia occurring in 85 patients treated between 1992 and 1994. Demographic factors, tumour‐related factors and clinical aspects of the episodes were correlated with outcome.

Results: The median age was 60 years (range, 18–87), with 56 (55%) episodes occurring in females. Twenty‐eight (27%) episodes occurred in patients with lymphoma, with the remaining 74 (73%) occurring in patients with solid tumours. At presentation, the median absolute neutrophil count (ANC) was 0.14×109/L with a median duration of significant neutropenia (ANC<0.5×10 9/L) of three days. The median duration of fever was two days. Twenty‐nine (28%) episodes had positive cultures; of these 11 had bacteraemia. Forty‐four (43%) episodes were classified as unexplained fevers. The remaining 29 episodes were associated with clinically documented infection but negative cultures. There was a high treatment success rate (81%) with first‐line empirical antibiotics. Of 19 treatment failures, 13 were due to the necessity for antibiotic modification; the other six patients died from infection. Factors associated with a worse outcome (including prolonged admission and death) include: diagnosis of lymphoma; increasing number of chemotherapy courses; early onset of neutropenia; pneumonia; severe hypotension; and multiple co‐morbidities.

Conclusions: Febrile neutropenia in adult patients with solid tumours or lymphoma is associated with a relatively good outcome, possibly due to the short duration of neutropenia. A future prospective study to validate the risk factors indentified in this study would be useful for defining patients at low risk for the adverse outcomes examined, in whom less intensive management for this condition may be possible.
Spinal cord excitatory amino acid receptors and plasma catecholamine autonomic responses in the conscious rabbit
Authors: Huang Wen , Hoffmann Nancy V. , West Malcolm J.
Published: March 2008

Intrathecal administration of the specific glutamate subtype receptor agonist NMDA (N‐methyl‐D‐aspartate), or the non‐NMDA receptor agonist AMPA (alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazoleproprionic acid), at the level of the lower thoracic spinal cord in the conscious rabbit, produces increased levels of plasma norepinephrine and a rise in blood pressure. These responses are specifically inhibited with prior intrathecal administration of the NMDA receptor antagonist AP‐5 (2‐amino‐5‐phosphonovaleric acid) or non‐NMDA receptor antagonist DNQX (6, 7‐dinitroquinoxaline‐2, 3‐dione), respectively. In contrast, arterial baroreflex activation induced by transient hypotension following intravenous sodium nitroprusside increases levels of plasma norepinephrine which are inhibited with intrathecal APS, but not DNQX. The experiments are consistent with glutamate acting as a neurotransmitter in the spinal cord influencing control of sympathetic nerve function via activation of spinal cord NMDA and non‐NMDA subtype receptors. The results support previous work suggesting that baroreflex function is predominantly mediated by spinal NMDA receptors and that spinal glutamate receptors are important in baroreflex control of the circulation.
Cholesterol and atherosc lerosis
Authors: Kroon Paulus A.
Published: March 2008

Cholesterol is an essential component of cellular membranes, but when present in excess in the circulation, can be deposited in the arterial wall, leading to the formation of atherosclerotic lesions. The principal plasma carrier of cholesterol, low density lipoprotein (LDL), is removed from the circulation by LDL receptors in the liver. This process plays a critical role in regulating plasma LDL levels. The unique structure and composition of the LDL particle makes it particularly susceptible to modification by oxidative reactions. Current evidence suggests that the production of oxidised LDL in the intima, and the removal of oxidised LDL particles by scavenger receptors on macrophages, play a central role in the development and progression of atherosclerotic lesions.
Congestive cardiac failure (CCF) as a cause of fatal stroke and all cause death
Authors: Jelinek M. V. , Ansari M. Z.
Published: March 2008

Background: Congestive cardiac failure (CCF) has been found to be a clinical risk factor for stroke in patients with non rheumatic atrial fibrillation.

Aims: To study CCF as a risk factor for stroke deaths and all cause deaths in coronary heart disease (CHD).

Methods: Case control study from a single cardiologist's practice: 370 deaths, 32 (9%) from stroke; controls of 160 and 370 consecutive patients for stroke deaths and all cause deaths respectively. Multivariate analysis using logistic regression.

Results: A‐Stroke deaths. Positive associations for CHD with CCF, hypertension; negative association for CHD without CCF. Patients with CHD and CCF were 7.4 times as likely to die from stroke as patients with CHD without CCF.

B—All cause deaths. Positive associations for CHD or cardiomyopathy with CCF, atrial fibrillation, diabetes and hypertension; negative association for CHD without CCF. Patients with CHD and CCF were 6.1 times as likely to die from all causes as patients with CHD without CCF.

Conclusions: Many stroke deaths in patients with CHD and CCF may be cardioembolic in origin. A randomised controlled trial in such patients is indicated to see if anticoagulants can reduce the incidence of stroke.
Commercial detailing techniques used by pharmaceutical representatives to influence prescribing
Authors: Roughead E. E. , Harvey K. J. , Gilbert A. L.
Published: March 2008

Aim: To determine the use of influence techniques by pharmaceutical representatives in their encounters with medical practitioners.

Method: We identified six influence techniques from the marketing literature which are thought to be commonly used by sales people. These have been termed the principles of reciprocity, friendship/liking, commitment/consistency, social validation, authority, and scarcity. We examined the use of these techniques by analysing audio‐recordings of pharmaceutical representatives' presentations to medical practitioners.

Results: Sixteen recordings, detailing 64 medicines, were obtained from seven medical practitioners. Reciprocation was the most commonly observed method of influence. Samples, gifts, printed material, patient information leaflets or invitations were offered in all encounters. Appeals to authority figures, where promotional claims were supported by reference to professors or specialists, specialist groups and specialist hospitals, were recorded. Social validation acts, where reference was made to the peer group were also common. Commitment acts were observed to occur in two ways; the first was as a direct request to use the product detailed and the second was as a series of questions or statements which gradually moved from pre‐agreed areas to solicitation of a commitment to prescribe the drug.

Conclusion: Influence techniques were found to be commonly used by pharmaceutical representatives when they detailed products to medical practitioners. Medical practitioners may not be aware of the potential effect these techniques can have on their prescribing practices. Knowledge of these techniques must be incorporated into educational programmes designed to provide health professionals with critical appraisal skills.
Comparison of atorvastatin alone versus simvastatin ± cholestyramine in the management of severe primary hypercholesterolemia (The Six Cities Study)
Authors: Simons L. A.
Published: March 2008

Background: Atorvastatin is a new member of the class of drugs which inhibit the enzyme Hydroxy‐Methylglutaryl Co‐A reductase, the rate limiting step in cholesterol biosynthesis.

Aim: To compare the effects of atorvastatin alone versus simvastatin±low dose resin (i.e. versus standard care) on low density lipoprotein (LDL) cholesterol in severe primary hypercholesterolaemia.

Methods: An open, multi‐centre, randomised study in patients previously stabilised on a cholesterol‐lowering diet and simvastatin 40 mg daily, having LDL cholesterol ≥5.0 mmol/L and triglycerides <4.0 mmol/L. After five weeks washout, 92 were randomised to receive atorvastatin 10 mg and 44 to receive simvastatin 10 mg. The dose was doubled every six weeks if LDL cholesterol remained ≥3.5 mmol/L. In accordance with manufacturers' recommendations, maximum dosage was atorvastatin 80 mg daily or simvastatin 40 mg daily (+cholestyramine 4 g daily in 84% of cases). Treatment was continued over 30 weeks. Lipids, lipoproteins, haematological and biochemical safety parameters were measured at regular intervals. Adverse events were monitored.

Results: Baseline LDL cholesterol was ∼9 ±2 mmol/L (SD). After 30 weeks treatment serum cholesterol reduction was 42±10% on atorvastatin versus 32±13% on simvas‐tatin±resin (p<0.001), LDL cholesterol reduction 49±12%versus 38±14% (plt;0.001), and triglyceride reduction 33±20%versus 25±22% (p<0.02). High density lipoprotein cholesterol increased by 7–10% on both treatments. The proportion of subjects achieving goal LDL cholesterol <3.5 mmol/L was two to three times greater in those on atorvastatin compared with those on simvastatin± resin at each titration point. Six patients on simvastatin and one on atorvastatin were withdrawn. The drugs were generally well tolerated and the pattern of adverse events was similar with either treatment.

Conclusions: Atorvastatin up to 80 mg daily appears to be an effective new treatment for the management of primary hypercholesterolaemia. It shows greater efficacy than simvastatin up to 40 mg daily±resin and has a similar safety profile.
Management of malignant pleural effusion
Authors: Tattersall M.
Published: March 2008

Malignant pleural effusion is a frequent cause of morbidity in cancer patients. Pleural aspiration relieves dyspnoea usually only for a matter of days, and if the tumour type is not chemosensitive, some form of pleurodesis is commonly required. Tube thoracostomy is widely used to achieve pleural drainage prior to attempting pleurodesis by instillation of a variety of ‘sclerosants’. Recently thoracoscopic instillation of talc has been advocated and some authors report high rates of fluid control. Randomised trials comparing this approach compared to lube thoracostomy and chemical pleurodesis are required.
Phase II trial of ifosfamide and cisplatinum in advanced ovarian cancer
Authors: Aziz Z. , Zahid M. , Ahmed Z. Vd Din , Arshad T.
Published: March 2008

To evaluate the efficacy of systemic ifosfamide, cisplatin (CDDP) combination as first line treatment followed by intraperitoneal (IP) chemotherapy with carboplatin (CBCDA) and etoposide as consolidation in patients with stage III and IV epithelial ovarian cancer.

A total of 40 patients with stage III and IV ovarian cancer were entered into the study. Ifosfamide 1 glm2 plus mesna 1 glm2 was given as six hour infusion daily for six days and CDDP 75 mglm2 was given on day seven. Patients completing six cycles of systemic therapy underwent second look laparotomy followed by four cycles of IP chemotherapy with CBCDA 300 mglm2 and etoposide 200 mglm2.

Of the 40 patients entering the protocol 27 patients completed six cycles with a complete remission (CR) of 65% and overall response of 67.5%. Twenty‐two patients underwent second look laparotomy with pathological CR in ten patients, microscopic disease in seven and macroscopic disease in five. Eleven patients completed four cycles of IP chemotherapy. At 52 months the overall survival (OS) was 36%. The disease free survival (DFS) at 45 months was 38%. Factors affecting OS were ascites (p<0.011), stage (p<0.04), weight change (p<0.017), residual disease (p<0.001), number of chemotherapy cycles (p<0.0001) and IP chemotherapy (p<0.006). Presently 35% patients are alive in CR, 15% are alive with disease, one patient has been lost to follow up while 47.5% have died. Of these four patients had progressive disease, seven relapsed, four died due to treatment related complications and two died in CR due to other causes. Subset analysis of 22 patients who had second look laparotomy and completed four cycles of IP chemotherapy revealed a distinct survival advantage.

IFOS+CDDP is an effective combination as first time treatment in advanced ovarian cancer. IP chemotherapy is effective as consolidation and seems to provide a significant survival advantage. Further studies with larger number of patients need to be done to confirm these results.
The role of ifosfamide in paediatric cancer
Authors: Advani S. H.
Published: March 2008

Ifosfamide is an active drug in the therapy of paediatric tumours such as rhabdomyosarcoma, Eivings' sarcoma, Wilms' tumour, neuroblastoma, germ cell tumours and lymphomas. Myelosuppression is the major toxicity along with haemorrhagic cystitis. The latter is largely prevented by the use of concomitant mesna.
Evaluation of a computer based package on electrocardiography
Authors: Devitt P. , Worthley S. , Palmer E. , Cehic D.
Published: March 2008

Background: Opportunities for interactive learning in electrocardiography are limited particularly at postgraduate level. In medical education, increasing use is being made of the electronic medium and various materials have been developed to improve clinicians’ skills.

Aims: To test and evaluate the learning of electrocardiography among health professionals.

Methods: A software package, containing a tutorial on electrocardiography and a self‐assessment programme of 140 electrocardiograms (ECGs) was constructed. Seventy‐two health professionals were recruited into the study and tested before and after the study period. Participants were randomly allocated to one of three groups: control (no study material), tutorial or computer. The tutorial group participated in a series of tutorials and the computer group were provided with a CD‐ROM containing study material for them to use in their own time. The results were assessed for statistical significance between all groups using analysis of variance techniques.

Results: Sixty‐one individuals completed the study. Each of the three groups was pre and post tested on their knowledge of electrocardiography and their ability to interpret ECGs. The computer group was the only group to achieve a significant increase in performance in their knowledge on electrocardiography and in their ability to interpret ECGs.

Conclusions: Suitably structured computer programmes are effective in helping clinicians understand electrocardiography and interpret ECGs.
Alteplase (r‐TPA) vs streptokinase
Authors: Hunt David
Published: March 2008

The GUSTO trial and an Australian consensus meeting in 1993 led to the recommendation that recombinant tissue plasminogen activator (r‐TPA) was the preferred thrombolytic in patients with acute myocardial infarction (AMI) and ST segment elevation under the age of 75, whose infarction was anterior, who could be treated within four hours of the onset of symptoms and who did not have a contraindication to thrombolysis. Available data suggest that streptokinase (SK) should not be administered in a patient who has received this drug three days or more previously.

New data on the risks of stroke confirm that the use of r‐TPA is associated with a higher risk of intracranial haemorrhage than SK, and those with a high risk profile for intracranial haemorrhage (hypertension and advanced age) should receive SK rather than r‐TPA.

It may be justified to give r‐TPA to any patient with a large infarct regardless of location, within four hours of the onset of infarction in an attempt to achieve TIMI flow grade 3 (complete) reperfusion, reduce mortality and improve left ventricular function and clinical outcomes. The focus for the future will be on how to treat more patients earlier with thrombolytic agents, rather than the choice of agent.
Thrombolytic eligibility
Authors: Ellis Christopher J. , French John K. , White Harvey D.
Published: March 2008

The Fibrinolytic Therapy Trialists’ Collaborative Group has demonstrated that patients without clear contraindications who present with ischaemic chest pain within 12 hours of the onset of symptoms and who have ST segment elevation or bundle branch block on their electrocardiogram (ECG), will benefit from thrombolytic therapy. Therefore the treatment of patients presenting with ischaemic chest pain is guided by the initial ECG. This paper addresses the question of thrombolytic eligibility in several subsets of patients who may benefit from treatment. It also explores the data which confirm the benefit for patients presenting with an inferior myocardial infarction and for those presenting from six‐12 hours after the onset of symptoms. In conclusion, thrombolytic therapy should not be routinely withheld from diabetic or elderly patients, menstruating women and patients who have had cardiopulmonary resuscitation.
Refining the risk‐benefit equation for thrombolysis: How to identify the low risk patient before administering thrombolytic therapy
Authors: Parsons Richard , Thompson Peter , Nidorf Mark , Hobbs Michael , Jamrozik Konrad
Published: March 2008

In view of the relative risk of intracranial haemorrhage and major bleeding with thrombolytic therapy, it is important to identify as early as possible the low risk patient who may not have a net clinical benefit from thrombolysis in the setting of acute myocardial infarction.

An analysis of 5434 hospital‐treated patients with myocardial infarction in the Perth MONICA study showed that age below 60 and absence of previous infarction or diabetes, shock, pulmonary oedema, cardiac arrest and Q‐wave or left bundle branch block on the initial ECG identified a large group of patients with a 28 day mortality of only 1 %, and one year mortality of only 2%. Identification of baseline risk in this way helps refine the risk‐benefit equation for thrombolytic therapy, and may help avoid unnecessary use of thrombolysis in those unlikely to benefit.
Hirudin (desirudin) and Hirulog (bivalirudin) in acute ischaemic syndromes and the rationale for the Hirulog/Early Reperfusion Occlusion (HERO 2) Study
Authors: White Harvey D. , Ellis Christopher J. , French John K. , Aylward Philip
Published: March 2008

Unlike unfractionated heparin, direct thrombin inhibitors such as hirudin and Hirulog inhibit clot‐bound as well as fluid‐phase thrombin, escape neutralisation by platelet secretion products, do not require monitoring, and are unassociated with immune thrombocytopenia. They have been shown to have modest advantages over heparin when given after thrombolytic therapy, reducing reinfarction by 14%. In the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO 2b) trial, patients treated with streptokinase and adjunctive hirudin had a reduction in death or myocardial infarction of 40% at 30 days (8.6% with hirudin versus 14.4% with heparin, p = 0.004). In the Hirulog Early Reperfusion/ Occlusion (HERO 1) trial, 48% of patients who received Hirulog as adjunctive therapy with streptokinase had Thrombolysis in Myocardial Infarction (TIMI) trial grade 3 flow in the infarct‐related artery, compared with 35% of patients who received heparin with streptokinase (p <0.05). The HERO 2 study, involving 17,000 patients, will test the hypothesis that Hirulog and aspirin given before streptokinase will reduce mortality compared with aspirin plus heparin. Early administration of direct thrombin inhibitors may potentially improve the outcome of patients treated with thrombolytic therapy.
Low molecular weight heparins in acute ischaemic syndromes
Authors: White Harvey D. , Ellis Christopher J. , French John K.
Published: March 2008

Thrombus formation and ongoing generation play a major role in the pathogenesis of unstable angina and myocardial infarction (MI). Unfractionated heparin is widely used as an adjunctive therapy in the management of acute ischaemic syndromes, but it has a number of limitations including inter‐patient variability, need for monitoring, and the fact that its use may be associated with thrombocytopenia.

Low molecular weight heparins have pharmacological and pharmacokinetic properties that may result in better clinical outcomes and safety. They are easy to administer and do not require monitoring. Low molecular weight heparins have been shown to reduce mortality and the incidence of MI and recurrent ischaemia compared with placebo in patients with unstable angina and non‐Q‐wave MI, and have a more predictable anticoagulant effect than standard unfractionated heparin. They also can be used long term in the outpatient setting, in the form of self‐administered subcutaneous injections.

The clinical relevance of these new developments is still being defined in ongoing clinical trials and cost‐effectiveness analyses.
Percutaneous transluminal coronary angioplasty (PTCA) without on‐site surgical facilities
Authors: Cheong Y. M. , Dick R. , Sia B. , Lim Y. L.
Published: March 2008

Background: Numerous publications from European and Canadian centres have documented the feasibility of performing percutaneous transluminal coronary angioplasty (PTCA) without on‐site surgical facilities. The absolute need for surgical standby has been changing especially with the introduction of coronary stent for bailout situations. This practice may be applicable in Australian centres especially in the environment of long waiting lists and cost containment.

Aim: To review the safety of performing PTCA by experienced operators in two Melbourne hospitals without on‐site surgical facilities.

Methods: We reviewed data of all patients who had PTCA electively (with low and moderate risks) between July 1996 and January 1997 and in the setting of acute myocardial infarction (AMI) from January 1996 to January 1997. Surgical standby was available as ‘next available room’ basis in nearby centres. Immediate outcome before discharge was documented and follow up from three to six months in 80% of all surviving patients.

Results: There were 46 elective PTCA and 41 PTCA for AMI. PTCA was successful in 82 (94%) patients. Among the elective cases, seven patients were already inpatients with unstable or postinfarct angina. Thirteen patients had stents deployed with three for acute closure. Abciximab (Reopro) was given to eight patients. Two patients had acute closure in the laboratory which could not be reopened, but did not require emergency coronary artery bypass grafting (CABG). There were four inhospital deaths (three related to AMI and one died of a noncoronary cause).

Conclusion: PTCA can be performed electively in a selected group of patients with coronary artery disease and as a primary procedure for AMI without on‐site surgical standby. (AustNZJMed 1998; 28: 165–171.)
KRAS codon 12 mutations in Australian non‐small cell lung cancer
Authors: Fong K. M. , Zimmerman P. V. , Smith P. J.
Published: March 2008

Background: In certain non‐small cell lung cancer (NSCLC) populations, codon 12 mutations of the KRAS oncogene comprising mostly G‐T transversions have diagnostic and prognostic value. However, it is not known if these findings are applicable to all populations of lung cancer patients.

Aims: To examine for KRAS codon 12 mutations in Australian NSCLC patients.

Methods: Tumour samples and corresponding normal lung tissue from 108 Australian patients with NSCLC undergoing curative resection were studied for mutations of KRAS codon 12 using a sensitive PCR assay. Mutations were confirmed by DNA sequencing and correlated with histological subtype, tumour stage, the presence of nodal metastases and survival.

Results: Eleven KRAS codon 12 mutations were detected in 108 NSCLCs, with most (8/11) occurring in the adenocarcinoma subtype (17% prevalence), but were not associated with adverse outcome or clinico‐pathological features. G‐T transversions were surprisingly infrequent (37% of adenocarcinoma mutations).

Conclusions: These data add to the evidence suggesting geographical differences in the spectrum and significance of KRAS codon 12 mutational genotypes in NSCLC. While these may be due to genetic variation and/or differences in carcinogen exposure, there is a need for larger population based studies before this potentially important biomarker can be recommended universally for optimising lung cancer management. (Aust NZ J Med 1998; 28: 184–189.)
Progress in management of acute myeloid leukaemia (AML) in Australia since 1980: a single institution retrospective study
Authors: Thomas D. M. , Seymour J. F. , Szer J. , Grigg A. P. , Basser R. L. , Green M. D. , Fox R. M.
Published: March 2008

Background: Much research has been conducted into the pathobiology, diagnosis, and management of acute myeloid leukaemia (AML) since 1980, with major contributions from Australian studies in this period.

Aims: To determine whether advances in basic and clinical research into AML have translated into improved survival for patients in the community.

Methods: A retrospective survey of records of all patients with AML presenting to the Royal Melbourne Hospital (RMH) over a 16 year period, analysed according to induction therapy and established prognostic factors. Between 1980 and December 1996 223 (98%) of 227 patients were evaluable.

ResuZts: The probability of survival at five years for patients treated since 1990 has improved significantly compared to the cohort treated between 1980‐89 (3455% vs 422%; meankstandard error). This benefit is most evident in patients less than 60 years of age (5057% vs 1124%). Successive induction protocols in the context of clinical trials conducted since 1985 contributed to improved outcomes. The selective application of bone marrow transplantation, and use of retinoic acid as induction therapy for acute promyelocytic leukaemia has also improved survival. Despite increases in dose‐intensity, early death rates for patients undergoing induction therapy fell during the study period.

Conclusions: Participation in clinical and basic research with the development of more intense and specific treatments for patients with AML has contributed to better outcomes, underpinned by improvements in supportive care. (Aust NZ J Med 1998; 28: 190‐1 96.)